Journal articles: 'Human Liver Stem Cells'

1

Thomas, David Brynmor. "The infusion of human fetal liver cells." Stem Cells 11, S1 (May 1993): 66–71. http://dx.doi.org/10.1002/stem.5530110614.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Jauregui, R. G., N. Fekete-Drimusz, C. Lipps, D. Wirth, M. P. Manns, F. W. R. Vondran, and M. Bock. "Mouse Liver Repopulation with Human Liver Stem Cells." Journal of Hepatology 64, no. 2 (2016): S154—S155. http://dx.doi.org/10.1016/s0168-8278(16)01655-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Schmelzer, Eva, Lili Zhang, Andrew Bruce, Eliane Wauthier, John Ludlow, Hsin-lei Yao, Nicholas Moss, et al. "Human hepatic stem cells from fetal and postnatal donors." Journal of Experimental Medicine 204, no. 8 (July 30, 2007): 1973–87. http://dx.doi.org/10.1084/jem.20061603.

Full text

Abstract:

Human hepatic stem cells (hHpSCs), which are pluripotent precursors of hepatoblasts and thence of hepatocytic and biliary epithelia, are located in ductal plates in fetal livers and in Canals of Hering in adult livers. They can be isolated by immunoselection for epithelial cell adhesion molecule–positive (EpCAM+) cells, and they constitute ∼0.5–2.5% of liver parenchyma of all donor ages. The self-renewal capacity of hHpSCs is indicated by phenotypic stability after expansion for >150 population doublings in a serum-free, defined medium and with a doubling time of ∼36 h. Survival and proliferation of hHpSCs require paracrine signaling by hepatic stellate cells and/or angioblasts that coisolate with them. The hHpSCs are ∼9 μm in diameter, express cytokeratins 8, 18, and 19, CD133/1, telomerase, CD44H, claudin 3, and albumin (weakly). They are negative for α-fetoprotein (AFP), intercellular adhesion molecule (ICAM) 1, and for markers of adult liver cells (cytochrome P450s), hemopoietic cells (CD45), and mesenchymal cells (vascular endothelial growth factor receptor and desmin). If transferred to STO feeders, hHpSCs give rise to hepatoblasts, which are recognizable by cordlike colony morphology and up-regulation of AFP, P4503A7, and ICAM1. Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies.

APA, Harvard, Vancouver, ISO, and other styles

4

Shafritz, David A., Mo R. Ebrahimkhani, and Michael Oertel. "Therapeutic Cell Repopulation of the Liver: From Fetal Rat Cells to Synthetic Human Tissues." Cells 12, no. 4 (February 6, 2023): 529. http://dx.doi.org/10.3390/cells12040529.

Full text

Abstract:

Progenitor cells isolated from the fetal liver can provide a unique cell source to generate new healthy tissue mass. Almost 20 years ago, it was demonstrated that rat fetal liver cells repopulate the normal host liver environment via a mechanism akin to cell competition. Activin A, which is produced by hepatocytes, was identified as an important player during cell competition. Because of reduced activin receptor expression, highly proliferative fetal liver stem/progenitor cells are resistant to activin A and therefore exhibit a growth advantage compared to hepatocytes. As a result, transplanted fetal liver cells are capable of repopulating normal livers. Important for cell-based therapies, hepatic stem/progenitor cells containing repopulation potential can be separated from fetal hematopoietic cells using the cell surface marker δ-like 1 (Dlk-1). In livers with advanced fibrosis, fetal epithelial stem/progenitor cells differentiate into functional hepatic cells and out-compete injured endogenous hepatocytes, which cause anti-fibrotic effects. Although fetal liver cells efficiently repopulate the liver, they will likely not be used for human cell transplantation. Thus, utilizing the underlying mechanism of repopulation and developed methods to produce similar growth-advantaged cells in vitro, such as human induced pluripotent stem cells (iPSCs). This approach has great translational potential for developing novel cell-based therapies in patients with liver disease. The present review gives a brief overview of the classic cell transplantation models and various cell sources studied as donor cell candidates. The advantages of fetal liver-derived stem/progenitor cells are discussed, as well as the mechanism of liver repopulation. Moreover, this article reviews the potential of in vitro developed synthetic human fetal livers from iPSCs and their therapeutic benefits.

APA, Harvard, Vancouver, ISO, and other styles

5

RUCK, P., J‐C XIAO, T. PIETSCH, and E. KAISERLING. "Hepatic stem cells in the human liver." Histopathology 29, no. 6 (December 1996): 590–91. http://dx.doi.org/10.1046/j.1365-2559.1996.d01-547.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

ROSKAMS, T., R. DE VOS, and V. DESMET. "Hepatic stem cells in the human liver." Histopathology 29, no. 6 (December 1996): 591–92. http://dx.doi.org/10.1046/j.1365-2559.1996.d01-548.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Zhou, Ping, Ryan Lahey, Daniel Cortes, Yetunde Olusanya, Sarah Hohm, Ha Tran, David Hess, and Jan A. Nolta. "Hepatocyte-Like Cells Can Be Derived from Human Umbilical Cord Blood and Embryonic Stem Cells: Tested in a Novel Mouse Model." Blood 112, no. 11 (November 16, 2008): 3490. http://dx.doi.org/10.1182/blood.v112.11.3490.3490.

Full text

Abstract:

Abstract Liver transplantation remains the only therapeutic option for many acute and chronic end-stage liver diseases. However, this approach is limited by a serious shortage of donor organs required for transplantation. Hepatocytes have been reported to be generated from cells not originated from liver, such as hematopoietic stem cells, mesenchymal stem cells and most recently embryonic stem cells. However, the frequency of these stem cell-derived hepatocytes is very low in most studies. Therefore, the significance of stem cell contribution to the repair of liver damage is still controversial. To further explore this potential, we used the beta-glucuronidase (GUSB)-null NOD/SCID/MPSVII mouse model for better identification of engrafted human cells. Enriched cord blood primitive cells (lineage depleted cells with high aldehyde dehydrogenase activity, ALDHhiLin−) were transplanted into irradiated NOD/SCID/MPSVII mice. One month after transplantation, carbon tetrachloride (CCl4) was administrated into the mice twice a week for 4 weeks to induce liver damage. In this model, ALDHhiLin− cells efficiently engrafted in the recipient mouse livers as demonstrated by GUSB positive immunohistological staining and the presence of human Alu DNA using PCR. The percentage of human cells in these livers ranged between 3% and 14.2% using quantitative real-time PCR. These engrafted cells improved recovery of the mice from toxic insult, and significantly increased the numbers of surviving mice. Furthermore, human liver-specific a-1-antitrypsin mRNA and albumin protein were expressed in the recipient livers. Interestingly, human vs. murine centromeric fluorescent in situ hybridization analysis on the liver sections demonstrated that most human cells were not fused to mouse cells. However, mouse nuclei were detected in the majority of the albumin-expressing cells, suggesting that fusion had occurred and was responsible for the appearance of donor derived hepatocyte-like cells. With the goal of achieving higher levels of liver reconstitution than had been possible using the adult stem cells, we began studying engraftment of human embryonic stem cells (hESC), which theoretically have the potential to regenerate any tissue. The H1 cell line was cultured on mouse embryonic fibroblasts then allowed to form embryoid bodies (EBs) in suspension culture for 7 days with or without further expansion and differentiation in attached culture for another month. EBs were dissociated into a single cell suspension and transplanted into NOD/SCID/MPSVII mice or NOD/SCID/IL2Rγ−/− mice via the tail vein after 300 RADs sublethal radiation with or without CCl4 administration. Two months post-transplantation, the human EB-derived cells were found to be well engrafted in the NOD/SCID/MPSVII mouse livers, spleens and kidneys, using the clear-cut enzymatic identification method for cells expressing normal levels of beta-glucuronidase in the mice, which are null for the enzyme. Human DNA was also detected in the recipient mouse liver. Most interestingly, human albumin-expressing cells were also found in the livers of engrafted mice. Our data indicate that the progeny of cord blood stem cells can significantly enhance survival of mice with severe liver damage, and that fusion can occur between transplanted and recipient cells. This could be a normal mechanism of liver repair, since hepatocytes exist normally as multinucleate cells. We also demonstrate that the progeny of hESC can be effectively dissociated and transplanted intravenously, then home to the liver and differentiate to the hepatocyte lineage in an immune deficient mouse model of liver damage.

APA, Harvard, Vancouver, ISO, and other styles

8

Najimi, Mustapha, Dung Ngoc Khuu, Philippe Antoine Lysy, Nawal Jazouli, Jorge Abarca, Christine Sempoux, and Etienne Marc Sokal. "Adult-Derived Human Liver Mesenchymal-Like Cells as a Potential Progenitor Reservoir of Hepatocytes?" Cell Transplantation 16, no. 7 (August 2007): 717–28. http://dx.doi.org/10.3727/000000007783465154.

Full text

Abstract:

It is currently accepted that adult tissues may develop and maintain their own stem cell pools. Because of their higher safety profile, adult stem cells may represent an ideal candidate cell source to be used for liver cell therapies. We therefore evaluated the differentiation potential of mesenchymal-like cells isolated from adult human livers. Mesenchymal-like cells were isolated from enzymatically digested adult human liver and expanded in vitro. Cell characterization was performed using flow cytometry, RT-PCR, and immunofluorescence, whereas the differentiation potential was evaluated both in vitro after incubation with specific media and in vivo after intrasplenic transplantation of uPA+/+-SCID and SCID mice. Adult-derived human liver mesenchymal-like cells expressed both hepatic and mesenchymal markers among which albumin, CYP3A4, vimentin, and α-smooth muscle actin. In vitro differentiation studies demonstrated that these mesenchymal-like cells are preferentially determined to differentiate into hepatocyte-like cells. Ten weeks following intrasplenic transplantation into uPA+/+-SCID mice, recipient livers showed the presence of human hepatocytic cell nodules positive for human albumin, prealbumin, and α-fetoprotein. In SCID transplanted liver mice, human hepatocyte-like cells were mostly found near vascular structures 56 days posttransplantation. In conclusion, the ability of isolated adult-derived liver mesenchymal stem-like cells to proliferate and differentiate into hepatocyte-like cells both in vitro and in vivo leads to propose them as an attractive expandable cell source for stem cell therapy in human liver diseases.

APA, Harvard, Vancouver, ISO, and other styles

9

Irudayaswamy, Antony, Mark Muthiah, Lei Zhou, Hau Hung, Nur Halisah Bte Jumat, Jamil Haque, Narcissus Teoh, et al. "Long-Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers." STEM CELLS 36, no. 1 (October 13, 2017): 103–13. http://dx.doi.org/10.1002/stem.2710.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Navarro-Tableros, Victor, Maria Beatriz Herrera Sanchez, Federico Figliolini, Renato Romagnoli, Ciro Tetta, and Giovanni Camussi. "Recellularization of Rat Liver Scaffolds by Human Liver Stem Cells." Tissue Engineering Part A 21, no. 11-12 (June 2015): 1929–39. http://dx.doi.org/10.1089/ten.tea.2014.0573.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Baek, Jin-Young, Yun-Hee Rhee, Kwang-Yul Cha, and Hyung-Min Chung. "Human Fetal Liver Derived Stem Cells Can Be Support the Maintenance of Human Embryonic Stem Cells." Blood 104, no. 11 (November 16, 2004): 4264. http://dx.doi.org/10.1182/blood.v104.11.4264.4264.

Full text

Abstract:

Abstract Prolonged propagation of human embryonic stem (ES) cells is currently achieved by co-culture with primary or immortalized mouse embryonic fibroblast (MEF) cells. In order to replace the heterologous with homologous co-culture systems, an attempt was made using mononuclear cells derived from human fetal liver. Human fetal liver-derived mesenchymal-like stem cells (FL-MLSC) can be maintained for the prolonged period of time. They showed the characteristics of mesenchymal stem cells in various aspects. They retained a normal diploid karyotype and growth characteristics over the successive culture. Human ES cells cultured on human FL-MLSC cells up to 8 passages displayed the unique morphology and molecular markers characteristic for undifferentiated human ES cells as cultured on MEF cells. Alkaline phosphatase activity was detected in human ES cells co-cultured on human FL-MLSC. Immunocytochemical analyses showed that expressions of stage-specific embryonic antigen-3, -4 and Oct-4 were not altered on human ES cells cultured on human FLDSC. Reverse-transcriptase PCR analyses showed that similar expressions of Oct-4 and Nanog genes, markers for undifferentiated ES cells, were also observed in human ES cells cultured on both human FL-MLSC and MEF cells. Furthermore, human ES cells cultured on human FL-MLSC retained unique differentiation potentials in culture when allowed to form embryoid body. Results of this study suggest that human FL-MLSC can support the maintenance of human ES cell in vitro.

APA, Harvard, Vancouver, ISO, and other styles

12

Yang, Chao, Lei Ji, Wen Yue, Shuang-Shuang Shi, Ruo-Yong Wang, Yan-Hua Li, Xiao-Yan Xie, et al. "Human Fetal Liver Stromal Cells Expressing Erythropoietin Promote Hematopoietic Development from Human Embryonic Stem Cells." Cellular Reprogramming 14, no. 1 (February 2012): 88–97. http://dx.doi.org/10.1089/cell.2011.0013.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Pourcher, Guillaume, Christelle Mazurier, Yé Yong King, Marie-Catherine Giarratana, Ladan Kobari, Daniela Boehm, Luc Douay, and Hélène Lapillonne. "Human Fetal Liver: AnIn VitroModel of Erythropoiesis." Stem Cells International 2011 (2011): 1–10. http://dx.doi.org/10.4061/2011/405429.

Full text

Abstract:

We previously described the large-scale production of RBCs from hematopoietic stem cells (HSCs) of diverse sources. Our present efforts are focused to produce RBCs thanks to an unlimited source of stem cells. Human embryonic stem (ES) cells or induced pluripotent stem cell (iPS) are the natural candidates. Even if the proof of RBCs production from these sources has been done, their amplification ability is to date not sufficient for a transfusion application. In this work, our protocol of RBC production was applied to HSC isolated from fetal liver (FL) as an intermediate source between embryonic and adult stem cells. We studied the erythroid potential of FL-derived CD34+cells. In thisin vitromodel, maturation that is enucleation reaches a lower level compared to adult sources as observed for embryonic or iP, but, interestingly, they (i) displayed a dramaticin vitroexpansion (100-fold more when compared to CB CD34+) and (ii) 100% cloning efficiency in hematopoietic progenitor assays after 3 days of erythroid induction, as compared to 10–15% cloning efficiency for adult CD34+cells. This work supports the idea that FL remains a model of study and is not a candidate forex vivoRBCS production for blood transfusion as a direct source of stem cells but could be helpful to understand and enhance proliferation abilities for primitive cells such as ES cells or iPS.

APA, Harvard, Vancouver, ISO, and other styles

14

Fomin, Marina E., Ashley I. Beyer, and Marcus O. Muench. "Human fetal liver cultures support multiple cell lineages that can engraft immunodeficient mice." Open Biology 7, no. 12 (December 2017): 170108. http://dx.doi.org/10.1098/rsob.170108.

Full text

Abstract:

During prenatal development the liver is composed of multiple cell types with unique properties compared to their adult counterparts. We aimed to establish multilineage cultures of human fetal liver cells that could maintain stem cell and progenitor populations found in the developing liver. An aim of this study was to test if maturation of fetal hepatocytes in short-term cultures supported by epidermal growth factor and oncostatin M can improve their ability to engraft immunodeficient mice. Fetal liver cultures supported a mixture of albumin + cytokertin-19 + hepatoblasts, hepatocytes, cholangiocytes, CD14 ++ CD32 + liver sinusoidal endothelial cells (LSECs) and CD34 + CD133 + haematopoietic stem cells. Transplantation of cultured cells into uPA-NOG or TK-NOG mice yielded long-term engraftment of hepatocytes, abundant LSEC engraftment and multilineage haematopoiesis. Haematopoietic engraftment included reconstitution of B-, T- and NK-lymphocytes. Colonies of polarized human hepatocytes were observed surrounded by human LSECs in contact with human CD45 + blood cells in the liver sinusoids. Thus, fetal liver cultures support multiple cell lineages including LSECs and haematopoietic stem cells while also promoting the ability of fetal hepatocytes to engraft adult mouse livers. Fetal liver cultures and liver-humanized mice created from these cultures can provide useful model systems to study liver development, function and disease.

APA, Harvard, Vancouver, ISO, and other styles

15

Ray, Katrina. "Functional miniature human liver generated from stem cells." Nature Reviews Gastroenterology & Hepatology 10, no. 8 (July 16, 2013): 443. http://dx.doi.org/10.1038/nrgastro.2013.128.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Fujino, Hisanori, Hidefumi Hiramatsu, Atsunori Tsuchiya, Haruyoshi Noma, Mitsutaka Shiota, Katsutsugu Umeda, Momoko Yoshimoto, Toshio Heike, Mamoru Ito, and Tatsutoshi Nakahata. "Use of the NOD/SCID/γcnull Mouse Model To Assess the Hepatocyte-Producing Ability of Human Hematopoietic Cells." Blood 106, no. 11 (November 16, 2005): 1695. http://dx.doi.org/10.1182/blood.v106.11.1695.1695.

Full text

Abstract:

Abstract Hematopoietic cells have been shown to generate nonhematopoietic cells, although the true plasticity of stem cells has been questioned. Here we used the NOD/SCID/γcnull mouse model, which permits efficient engraftment of human hematopoietic stem cells and their multi-lineage differentiation including T cells, to investigate whether human hematopoietic stem cells can differentiate into human hepatocytes. Freshly collected cord blood was depleted of phagocytes with Silica® followed by CD34 positive selection using auto MACS®. These cells were intravenously transplanted into irradiated mice, after which the liver was either undamaged or damaged by chemicals. The livers of these mice contained hepatocyte-specific (albumin, CYP family, TAT, alpha1AT, CPSI, prealbumin, transferrin and RBP4), cholangiocyte-specific (CK19) and vascular endothelial cell-specific (eNOS) human mRNAs. Immunohistochemistry detected the human hepatocyte specific antigens, albumin and alpha-1-antitrypsin-positive hepatocytes, cholangiocytes and CD68+ Kupffer cells. We also found human albumin in the murine bloodstream. Human albumin levels in the peripheral blood of transplanted mice correlate with the degree of PB chimerism and increase with time after transplantation. Furthermore, after obtaining liver cells by collagenase perfusion, flow cytometry revealed the presence of human albumin-positive cells that bear both human and murine MHC molecules, suggesting cell fusion occurs. All of the above phenomena were found in both liver-damaged and undamaged mice. In addition, we found human CD34+ cells are recruited from the murine bone marrow to the liver only in the case of acute liver injury but do not acquire hepatic stem/progenitor characteristics. Our observation suggests there are two pathways that yield hepatic cells from hematopoietic stem cells. The first requires liver damage that recruits CD34+ cells from the bone marrow via the circulation while the second pathway does not involve liver damage and appears to represent a constitutive default pathway of hematopoietic to nonhematopoietic transition. Our model is thus a versatile tool for investigating the development of functional human hepatic cells from hematopoietic cells and the feasibility of using hematopoietic cells in clinical situations.

APA, Harvard, Vancouver, ISO, and other styles

17

Rogler, Charles E., Remon Bebawee, Joe Matarlo, Joseph Locker, Nicole Pattamanuch, Sanjeev Gupta, and Leslie E. Rogler. "Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver." Journal of Histochemistry & Cytochemistry 65, no. 1 (November 24, 2016): 33–46. http://dx.doi.org/10.1369/0022155416675153.

Full text

Abstract:

Recent investigations have reported many markers associated with human liver stem/progenitor cells, “oval cells,” and identified “niches” in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver. We identified large clusters of disorganized, FOXA2 expressing, oval cells in localized liver regions surrounded by fibrotic matrix, designated as “micro-niches.” Specific FOXA2-positive cells within the micro-niches organize into primitive duct structures that support both hepatocytic and bile ductular differentiation enabling identification of entire lineages of cells forming the two types of structures. We also detected expression of hsa-miR-122 in primitive ductular reactions expected for hepatocytic differentiation and hsa-miR-23b cluster expression that drives liver cell fate decisions in cells undergoing lineage commitment. Our data establish the foundation for a mechanistic hypothesis on how stem cell lineages progress in specialized micro-niches in cirrhotic end-stage liver disease.

APA, Harvard, Vancouver, ISO, and other styles

18

Kung, Janet W. C., Ian S. Currie, Stuart J. Forbes, and James A. Ross. "Liver Development, Regeneration, and Carcinogenesis." Journal of Biomedicine and Biotechnology 2010 (2010): 1–8. http://dx.doi.org/10.1155/2010/984248.

Full text

Abstract:

The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

APA, Harvard, Vancouver, ISO, and other styles

19

Kuijk, Ewart, Francis Blokzijl, Myrthe Jager, Nicolle Besselink, Sander Boymans, Susana M. Chuva de Sousa Lopes, Ruben van Boxtel, and Edwin Cuppen. "Early divergence of mutational processes in human fetal tissues." Science Advances 5, no. 5 (May 2019): eaaw1271. http://dx.doi.org/10.1126/sciadv.aaw1271.

Full text

Abstract:

A developing human fetus needs to balance rapid cellular expansion with maintaining genomic stability. Here, we accurately quantified and characterized somatic mutation accumulation in fetal tissues by analyzing individual stem cells from human fetal liver and intestine. Fetal mutation rates were about fivefold higher than in tissue-matched adult stem cells. The mutational landscape of fetal intestinal stem cells resembled that of adult intestinal stem cells, while the mutation spectrum of fetal liver stem cells is distinct from stem cells of the fetal intestine and the adult liver. Our analyses indicate that variation in mutational mechanisms, including oxidative stress and spontaneous deamination of methylated cytosines, contributes to the observed divergence in mutation accumulation patterns and drives genetic mosaicism in humans.

APA, Harvard, Vancouver, ISO, and other styles

20

Zhou, Ping, Sara Hohm, David A. Hess, and Jan A. Nolta. "Liver Engraftment by Transplanted Human Progenitor Cells with High Aldehyde Dehydrogenase Activity in a Novel Model, NOD/SCID/MPSVII Mice." Blood 110, no. 11 (November 16, 2007): 434. http://dx.doi.org/10.1182/blood.v110.11.434.434.

Full text

Abstract:

Abstract Hematopoietic stem cells (HSC) have been reported to generate cells other than the blood lineage and thus hold enormous promise for repairing damaged tissues. Evidence from our lab and others suggests that hepatocytes can be derived from HSC. However, the frequency of HSC-derived hepatocytes varies tremendously among various studies which use different stem cell subsets and different mouse models. Therefore, the significance of hematopoietic stem cell contribution to the repair of liver damage is still controversial. To further explore this potential, we used the beta-glucuronidase (GUSB)-deficient NOD/SCID/MPSVII mouse model for better identification of engrafted human cells. We and others have previously shown that lineage depleted (lin−) human umbilical cord blood-derived cells with high aldehyde dehydrogenase activity (ALDHhi) are enriched for primitive HSC. In the current studies, ALDHhi lin− cells were transplanted into irradiated NOD/SCID/MPSVII mice. One month after transplantation, carbon tetrachloride (CCl4) was administrated into the mice twice a week for 4 weeks to induced liver damage. In this model, ALDHhi lin− cells gave rise to robust hematopoietic reconstitution (71%±13.1 in bone marrow, 12.8%±4% in peripheral blood and 10.7%±8.8% in spleen) while ALDHlolin− cells failed to engraft. In the liver, engraftment of human cells in mice tansplanted with ALDHhi lin− cells was demonstrated by the presence of human Alu DNA using PCR. CD45+ cells were detected by both FACS (2.11%±1.1) and by immunohistological staining in the liver sections. GUSB expression was frequently evident in kuffer cells adjacent to blood vessels and to a lesser extent in the liver parenchyma. GUSB+ cells were more abundant than CD45+ cells. Most interestingly, human liver-specific a-1-antitrypsin mRNA was detected in the recipient murine livers by RT-PCR analysis. Human albumin- expressing cells were also found in these livers, although such cells were rare as compared to human CD45+ or GUSB+ cells. In contrast, human cells were not detected in the livers of mice tansplanted with ALDHlolin− cells in any of our assays. Thus, ALDH-expressing progenitor cells demonstrated potent engraftment of variable cellular phenotypes, suggesting that these adult progenitor cells should be further explored in transplantation models of tissue damage. Our data also support the idea that hematopoietic stem cells may home to the injured liver and release trophic factors that hasten tissue repair, while direct differentiation of these stem cells to hepatocytes or fusion of these cells with hepatocytes is rare and contributes to a lesser extent to liver repair.

APA, Harvard, Vancouver, ISO, and other styles

21

Grandy, Rodrigo, Rute A. Tomaz, and Ludovic Vallier. "Modeling Disease with Human Inducible Pluripotent Stem Cells." Annual Review of Pathology: Mechanisms of Disease 14, no. 1 (January 24, 2019): 449–68. http://dx.doi.org/10.1146/annurev-pathol-020117-043634.

Full text

Abstract:

Understanding the physiopathology of disease remains an essential step in developing novel therapeutics. Although animal models have certainly contributed to advancing this enterprise, their limitation in modeling all the aspects of complex human disorders is one of the major challenges faced by the biomedical research field. Human induced pluripotent stem cells (hiPSCs) derived from patients represent a great opportunity to overcome this deficiency because these cells cover the genetic diversity needed to fully model human diseases. Here, we provide an overview of the history of hiPSC technology and discuss common challenges and approaches that we and others have faced when using hiPSCs to model disease. Our emphasis is on liver disease, and consequently, we review the progress made using this technology to produce functional liver cells in vitro and how these systems are being used to recapitulate a diversity of developmental, metabolic, genetic, and infectious liver disorders.

APA, Harvard, Vancouver, ISO, and other styles

22

Wang, Xiuli, Shundi Ge, George McNamara, Qian-Lin Hao, Gay M. Crooks, and Jan A. Nolta. "Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells." Blood 101, no. 10 (May 15, 2003): 4201–8. http://dx.doi.org/10.1182/blood-2002-05-1338.

Full text

Abstract:

AbstractRodent bone marrow cells can contribute to liver. If these findings are applicable to humans, marrow stem cells could theoretically be harvested from a patient and used to repair his/her damaged liver. To explore this potential, CD34+ or highly purified CD34+CD38−CD7− human hematopoietic stem cells from umbilical cord blood and bone marrow were transplanted into immunodeficient mice. One month after transplantation, carbon tetrachloride (CCl4) was administered into the mice to induce liver damage and hepatocyte proliferation. Mice were analyzed in comparison with CCl4-injured mice that did not receive transplants and noninjured controls that received transplants with the same stem cell populations, one month after liver damage. Human-specific albumin mRNA and protein were expressed in the mouse liver and human albumin was detected in the serum of mice that had received CCl4 injury. Human alpha-fetoprotein was never expressed, but in some mice, human cytokeratin 19 was expressed, which may indicate bile duct development in addition to the albumin-secreting hepatocyte-like cells. Human albumin was not expressed in the starting stem cell populations in injured mice that did not receive transplants nor in noninjured mice that had received transplants of human stem cells. Human albumin expression was detected only in CCl4-treated mice that received transplants of human stem cells, and recovery was increased by administration of human hepatocyte growth factor 48 hours after the CCl4-mediated liver injury. Our studies provide evidence that human “hematopoietic” stem/progenitor cell populations have the capacity to respond to the injured liver microenvironment by inducing albumin expression.

APA, Harvard, Vancouver, ISO, and other styles

23

Michalopoulos, George K., and Zahida Khan. "Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease." Gastroenterology 149, no. 4 (October 2015): 876–82. http://dx.doi.org/10.1053/j.gastro.2015.08.004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Dalgetty, Donna M., Claire N. Medine, John P. Iredale, and David C. Hay. "Progress and future challenges in stem cell-derived liver technologies." American Journal of Physiology-Gastrointestinal and Liver Physiology 297, no. 2 (August 2009): G241—G248. http://dx.doi.org/10.1152/ajpgi.00138.2009.

Full text

Abstract:

The emergence of regenerative medicine has led to significant advances in the identification and understanding of human stem cells and adult progenitor cells. Both cell populations exhibit plasticity and theoretically offer a potential source of somatic cells in large numbers. Such a resource has an important role to play in the understanding of human development, in modeling human disease and drug toxicity, and in the generation of somatic cells in large numbers for cell-based therapies. Presently, liver transplantation is the only effective treatment for end-stage liver disease. Although this procedure can be carried out with high levels of success, the routine transplant of livers is severely limited by organ donor availability. As a result, attention has focused on the ability to restore liver mass and function by alternative approaches ranging from the bioartificial device to transplantation of human hepatocytes. In this review we will focus on the generation of human hepatic endoderm from different stem/progenitor cell populations with a view to its utility in regenerative medicine.

APA, Harvard, Vancouver, ISO, and other styles

25

Li, Jing, Feiyue Xing, Feng Chen, Liumin He, Kwok-Fai So, Yingxia Liu, and Jia Xiao. "Functional 3D Human Liver Bud Assembled from MSC-Derived Multiple Liver Cell Lineages." Cell Transplantation 28, no. 5 (June 13, 2018): 510–21. http://dx.doi.org/10.1177/0963689718780332.

Full text

Abstract:

The severe shortage of donor liver organs requires the development of alternative methods to provide transplantable liver tissues such as stem cell-derived organoids. Despite several studies describing the generation of vascularized and functional liver tissues, none have succeeded in assembling human liver buds containing hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs). Here, we report a reproducible, easy-to-follow, and comprehensive self-assembly protocol to generate three-dimensional (3D) human liver buds from naïve mesenchymal stem cells (MSCs), MSC-derived hepatocytes, and HSC- and LSEC-like cells. By optimizing the ratio between these different cell lineages, the cell mixture self-assembled into 3D human liver buds within 72 h in vitro, and exhibited similar characteristics with early-stage murine liver buds. In a murine model of acute liver failure, the mesenteric transplantation of self-assembled human liver buds effectively rescued animal death, and triggered hepatic ameliorative effects that were better than the ones observed after splenic transplantation of human hepatocytes or naïve MSCs. In addition, transplanted human liver buds underwent maturation during injury alleviation, after which they exhibited a gene expression profile signature similar to the one of adult human livers. Collectively, our protocol provides a promising new approach for the in vitro construction of functional 3D human liver buds from multiple human MSC-derived hepatic cell lineages; this new technique would be useful for clinical transplantation and regenerative medicine research.

APA, Harvard, Vancouver, ISO, and other styles

26

Kholodenko, Irina V., Leonid K. Kurbatov, Roman V. Kholodenko, Garik V. Manukyan, and Konstantin N. Yarygin. "Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?" Cells 8, no. 10 (September 22, 2019): 1127. http://dx.doi.org/10.3390/cells8101127.

Full text

Abstract:

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.

APA, Harvard, Vancouver, ISO, and other styles

27

Abkowitz, Janis L. "Can Human Hematopoietic Stem Cells Become Skin, Gut, or Liver Cells?" New England Journal of Medicine 346, no. 10 (March 7, 2002): 770–72. http://dx.doi.org/10.1056/nejm200203073461012.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Lee, Jooyoung, Jiwan Choi, Seoon Kang, Jiye Kim, Ryunjin Lee, Seongjun So, Young-In Yoon, et al. "Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells." Cells 9, no. 6 (June 22, 2020): 1521. http://dx.doi.org/10.3390/cells9061521.

Full text

Abstract:

Human liver-derived stem cells (hLD-SCs) have been proposed as a possible resource for stem cell therapy in patients with irreversible liver diseases. However, it is not known whether liver resident hLD-SCs can differentiate toward a hepatic fate better than mesenchymal stem cells (MSCs) obtained from other origins. In this study, we compared the differentiation ability and regeneration potency of hLD-SCs with those of human umbilical cord matrix-derived stem cells (hUC-MSCs) by inducing hepatic differentiation. Undifferentiated hLD-SCs expressed relatively high levels of endoderm-related markers (GATA4 and FOXA1). During directed hepatic differentiation supported by two small molecules (Fasudil and 5-azacytidine), hLD-SCs presented more advanced mitochondrial respiration compared to hUC-MSCs. Moreover, hLD-SCs featured higher numbers of hepatic progenitor cell markers on day 14 of differentiation (CPM and CD133) and matured into hepatocyte-like cells by day 7 through 21 with increased hepatocyte markers (ALB, HNF4A, and AFP). During in vivo cell transplantation, hLD-SCs migrated into the liver of ischemia-reperfusion injury-induced mice within 2 h and relieved liver injury. In the thioacetamide (TAA)-induced liver injury mouse model, transplanted hLD-SCs trafficked into the liver and spontaneously matured into hepatocyte-like cells within 14 days. These results collectively suggest that hLD-SCs hold greater hepatogenic potential, and hepatic differentiation-induced hLD-SCs may be a promising source of stem cells for liver regeneration.

APA, Harvard, Vancouver, ISO, and other styles

29

Lee, Sang Woo, Jae Uk Chong, Seon Ok Min, Seon Young Bak, and Kyung Sik Kim. "Are Adipose-Derived Stem Cells from Liver Falciform Ligaments Another Possible Source of Mesenchymal Stem Cells?" Cell Transplantation 26, no. 5 (May 2017): 855–66. http://dx.doi.org/10.3727/096368916x693833.

Full text

Abstract:

Falciform ligaments in the liver are surrounded by adipose tissue. We investigated the capability of adipose-derived stem cells from human liver falciform ligaments (hLF-ADSCs) to differentiate into hepatic-type cells and confirmed the functional capacity of the cells. Mesenchymal stem cells (MSCs) were isolated from the liver falciform ligament and abdominal subcutaneous adipose tissue in patients undergoing partial hepatectomy for liver disease. Cells were cultivated in MSC culture medium. Properties of MSCs were confirmed by flow cytometry, RT-PCR analysis, immunocytochemistry assays, and multilineage differentiation. Hepatic induction was performed using a three-step differentiation protocol with various growth factors. Morphology, capacity for expansion, and characteristics were similar between hLF-ADSCs and adipose-derived stem cells from human abdominal subcutaneous adipose tissue (hAS-ADSCs). However, hematopoietic– and mesenchymal–epithelial transition (MET)-related surface markers (CD133, CD34, CD45, and E-cadherin) had a higher expression in hLF-ADSCs. The hepatic induction marker genes had a higher expression in hLF-ADSCs on days 7 and 10 after the hepatic induction. Albumin secretion was similar between hLF-ADSCs and hAS-ADSCs at 20 days after the hepatic induction. The hLF-ADSCs had a different pattern of surface marker expression relative to hAS-ADSCs. However, proliferation, multilineage capacity, and hepatic induction were similar between the cell types. Accordingly, it may be a useful source of MSCs for patients with liver disease.

APA, Harvard, Vancouver, ISO, and other styles

30

Saidi, Reza, R. Rajeshkumar, A. Shariftabrizi, A. Zimmerman, and O. Walter. "Human Adipose-Derived Mesenchymal Stem Cells Promote Liver Regeneration." Journal of Investigative Surgery 28, no. 6 (July 23, 2015): 303–8. http://dx.doi.org/10.3109/08941939.2015.1006379.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Zhou, Ping, Louisa Wirthlin, Jeannine McGee, Geralyn Annett, and Jan Nolta. "Contribution of human hematopoietic stem cells to liver repair." Seminars in Immunopathology 31, no. 3 (June 17, 2009): 411–19. http://dx.doi.org/10.1007/s00281-009-0166-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Ratti, R., N. Saulnier, F. Colombo, L. Porretti, A. Cattaneo, M. A. Puglisi, G. Rossi, G. Piccolo, B. Foglieni, and D. Prati. "Characterization of mesenchymal stem cells-like in human liver." Digestive and Liver Disease 40, no. 5 (May 2008): A14. http://dx.doi.org/10.1016/j.dld.2007.12.048.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Chung, Hyung-Min, Yun-Hee Rhee, Kwang-Yul Cha, and Jin-Young Baek. "Establishment and Characterization of Human Fetal Liver Derived Stem Cell Line." Blood 104, no. 11 (November 16, 2004): 4265. http://dx.doi.org/10.1182/blood.v104.11.4265.4265.

Full text

Abstract:

Abstract Mesenchymal stem cells (MSC) have been derived from different sources, including bone marrow and liver. To further support the hypothesis that MSC may also exist in most postnatal tissues, we isolated a clonogenic, multipotent, rapidly proliferating population of cells from a fetal liver and defined them as mesenchymal-like stem cells (FL-MLSC) derived from human fetal liver. In this study, FACS analysis showed that FL-MLSC are positive for CD105 (endoglin/SH-2), CD73 (5′ terminal nucleotidase/SH-3), CD166 (ALCAM-1), CD44 (the hyaluronate receptor), HLA class-I(HLA-ABC), CDw90 (thy-1), CD13, and CD106 but negative for CD34 and HLA class-II(HLA-DR). Cell-cycle analysis showed that more than 81.9% cells were arrested in G0 and G1 phases, whereas an only small subpopulation of cells was actively engaged in proliferation (S + G2 + M = 18%) and doubling in about 48 hours. FL-MLSC retained normal diploid karyotypes and growth characteristics over the successive culture. In addition, under differentiation culture conditions, these cells showed the capability of differentiation into various cell types including chondrogenic, adipogenic, osteogenic, neuronal and endocrine lineages. These results demonstrated that FL-MLSC could be isolated from human fetal livers by means of their adherent ability and suggested that they were capable of self-renewal and multipotent differentiation.

APA, Harvard, Vancouver, ISO, and other styles

34

Sonoyama, Takuhiro, Masakatsu Sone, Kyoko Honda, Daisuke Taura, Katsutoshi Kojima, Megumi Inuzuka, Naotetsu Kanamoto, Naohisa Tamura, and Kazuwa Nakao. "Differentiation of Human Embryonic Stem Cells and Human Induced Pluripotent Stem Cells into Steroid-Producing Cells." Endocrinology 153, no. 9 (September 1, 2012): 4336–45. http://dx.doi.org/10.1210/en.2012-1060.

Full text

Abstract:

Although there have been reports of the differentiation of mesenchymal stem cells and mouse embryonic stem (ES) cells into steroid-producing cells, the differentiation of human ES/induced pluripotent stem (iPS) cells into steroid-producing cells has not been reported. The purpose of our present study was to establish a method for inducing differentiation of human ES/iPS cells into steroid-producing cells. The first approach we tried was embryoid body formation and further culture on adherent plates. The resultant differentiated cells expressed mRNA encoding the steroidogenic enzymes steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, cytochrome P450-containing enzyme (CYP)-11A1, CYP17A1, and CYP19, and secreted progesterone was detected in the cell medium. However, expression of human chorionic gonadotropin was also detected, suggesting the differentiated cells were trophoblast like. We next tried a multistep approach. As a first step, human ES/iPS cells were induced to differentiate into the mesodermal lineage. After 7 d of differentiation induced by 6-bromoindirubin-3′-oxime (a glycogen synthase kinase-3β inhibitor), the human ES/iPS cells had differentiated into fetal liver kinase-1- and platelet derived growth factor receptor-α-expressing mesodermal lineage cells. As a second step, plasmid DNA encoding steroidogenic factor-1, a master regulator of steroidogenesis, was introduced into these mesodermal cells. The forced expression of steroidogenic factor-1 and subsequent addition of 8-bromoadenosine 3′,5′-cyclic monophosphate induced the mesodermal cells to differentiate into the steroidogenic cell lineage, and expression of CYP21A2 and CYP11B1, in addition to steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, CYP11A1, and CYP17A1, was detected. Moreover, secreted cortisol was detected in the medium, but human chorionic gonadotropin was not. These findings indicate that the steroid-producing cells obtained through the described multistep method are not trophoblast like; instead, they exhibit characteristics of adrenal cortical cells.

APA, Harvard, Vancouver, ISO, and other styles

35

Sato, Yasushi, Hironobu Araki, Junji Kato, Kiminori Nakamura, Yutaka Kawano, Masayoshi Kobune, Tsutomu Sato, et al. "Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion." Blood 106, no. 2 (July 15, 2005): 756–63. http://dx.doi.org/10.1182/blood-2005-02-0572.

Full text

Abstract:

Abstract Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers. (Blood. 2005;106:756-763)

APA, Harvard, Vancouver, ISO, and other styles

36

Al Battah, Feras, Joery De Kock, Tamara Vanhaecke, and Vera Rogiers. "Current Status of Human Adipose–Derived Stem Cells: Differentiation into Hepatocyte-Like Cells." Scientific World JOURNAL 11 (2011): 1568–81. http://dx.doi.org/10.1100/tsw.2011.146.

Full text

Abstract:

The shortage of human organ donors and the low cell quality of available liver tissues represent major obstacles for the clinical application of orthotropic liver transplantation and hepatocyte transplantation, respectively. Therefore, worldwide research groups are investigating alternative extrahepatic cell sources. Recentin vitrostudies have demonstrated that mesenchymal stem cells (MSCs) from various sources, including human bone marrow, adipose tissue, and umbilical cord, can be differentiated into hepatocyte-like cells when appropriate conditions are used. In particular, interest exists for human adipose–derived stems cells (hASCs) as an attractive cell source for generating hepatocyte-like cells. The hASCs are multipotent MSCs that reside in adipose tissue, with the ability to self-renew and differentiate into multiple cell lineages. Moreover, these cells can secrete multiple growth factors and cytokines that exert beneficial effects on organ or tissue injury. In this review, we will not only present recent data regarding hASC biology, their isolation, and differentiation capability towards hepatocytes, but also the potential application of hASC-derived hepatocytes to study drug toxicity. Additionally, this review will discuss the therapeutic potential of hASCs as undifferentiated cells in liver regeneration.

APA, Harvard, Vancouver, ISO, and other styles

37

El-Kehdy, Hoda, Guillaume Pourcher, Wenwei Zhang, Zahia Hamidouche, Sylvie Goulinet-Mainot, Etienne Sokal, Pierre Charbord, Mustapha Najimi, and Anne Dubart-Kupperschmitt. "Hepatocytic Differentiation Potential of Human Fetal Liver Mesenchymal Stem Cells:In VitroandIn VivoEvaluation." Stem Cells International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/6323486.

Full text

Abstract:

In line with the search of effective stem cell population that would progress liver cell therapy and because the rate and differentiation potential of mesenchymal stem cells (MSC) decreases with age, the current study investigates the hepatogenic differentiation potential of human fetal liver MSCs (FL-MSCs). After isolation from 11-12 gestational weeks’ human fetal livers, FL-MSCs were shown to express characteristic markers such as CD73, CD90, and CD146 and to display adipocytic and osteoblastic differentiation potential. Thereafter, we explored their hepatocytic differentiation potential using the hepatogenic protocol applied for adult human liver mesenchymal cells. FL-MSCs differentiated in this way displayed significant features of hepatocyte-like cells as demonstratedin vitroby the upregulated expression of specific hepatocytic markers and the induction of metabolic functions including CYP3A4 activity, indocyanine green uptake/release, and glucose 6-phosphatase activity. Following transplantation, naive and differentiated FL-MSC were engrafted into the hepatic parenchyma of newborn immunodeficient mice and differentiatedin situ. Hence, FL-MSCs appeared to be interesting candidates to investigate the liver development at the mesenchymal compartment level. Standardization of their isolation, expansion, and differentiation may also support their use for liver cell-based therapy development.

APA, Harvard, Vancouver, ISO, and other styles

38

Yong, Kylie Su Mei, Choong Tat Keng, Shu Qi Tan, Eva Loh, Kenneth TE Chang, Thiam Chye Tan, Wanjin Hong, and Qingfeng Chen. "Human CD34loCD133lo fetal liver cells support the expansion of human CD34hiCD133hi hematopoietic stem cells." Cellular & Molecular Immunology 13, no. 5 (May 25, 2015): 605–14. http://dx.doi.org/10.1038/cmi.2015.40.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Sugawara, Takeaki, and Atsushi Iwama. "Impaired Repopulating Activity of Fus-Deficient Hematopoietic Stem Cells." Blood 110, no. 11 (November 16, 2007): 2222. http://dx.doi.org/10.1182/blood.v110.11.2222.2222.

Full text

Abstract:

Abstract RNA-binding protein FUS (also known as TLS) was originally identified in chromosomal translocation in human myxoid liposarcoma. The FUS gene is also translocated with the transcription factor gene ERG in human myeloid leukemia with recurrent chromosomal translocation t(16;21). Multiple data suggest that wild-type FUS is also involved in the development of leukemia as one of the downstream targets for oncoproteins including BCR-ABL. However, little is known about the role of FUS in the normal hematopoiesis. The previous report demonstrated that Fus-deficient (Fus−/−) newborn mice, which die shortly after birth because they cannot suckle, have a non-cell-autonomous defect in B lymphocyte development. No cell-autonomous defect of Fus−/− hematopoietic cells has been documented. Here we report the detailed analyses of the Fus−/− fetal liver hematopoietic stem cells (HSCs). Fus−/− fetal livers at embryonic day 14.5 were smaller in size and exhibited a significant reduction in hematopoietic cell numbers by 60% compared with the wild type (WT). Nonetheless, no significant difference was observed in the proportion of stem/progenitor cell fraction (lineage-marker-c-Kit+Sca-1+; KSL) as well as colony-forming cells between WT and Fus−/− fetal livers. Fus−/− KSL cells proliferated and differentiated almost normally in vitro. To examine in vivo repopulating activity, we transplanted fetal liver cells to lethally irradiated CD45.1 recipients with competitor bone marrow cells. Fus−/− fetal liver donor cells reconstituted recipients’ hematopoiesis for the long term and contributed to all cell lineages including B lymphocytes. In contrast to the in vitro results, however, the chimerism of donor-derived cells was significantly lower in recipients receiving Fus−/− fetal liver cells compared with WT controls (approximately 2-fold reduction). This trend was reproducible with both unfractionated and purified KSL fetal liver test cells. Our data demonstrated that the proto-oncogene Fus is involved in the maintenance of normal HSC functions. Detailed analyses on the underlying mechanisms are in progress.

APA, Harvard, Vancouver, ISO, and other styles

40

Herrera, Maria Beatriz, Valentina Fonsato, Stefania Bruno, Cristina Grange, Nicholas Gilbo, Renato Romagnoli, Ciro Tetta, and Giovanni Camussi. "Human liver stem cells improve liver injury in a model of fulminant liver failure." Hepatology 57, no. 1 (January 2013): 311–19. http://dx.doi.org/10.1002/hep.25986.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Almeida-Porada, Graça, Christopher D. Porada, Jason Chamberlain, Ali Torabi, and Esmail D. Zanjani. "Formation of human hepatocytes by human hematopoietic stem cells in sheep." Blood 104, no. 8 (October 15, 2004): 2582–90. http://dx.doi.org/10.1182/blood-2004-01-0259.

Full text

Abstract:

Abstract We took advantage of the proliferative and permissive environment of the developing preimmune fetus to develop a noninjury large animal model in sheep, in which the transplantation of defined populations of human hematopoietic stem cells resulted in the establishment of human hematopoiesis and led to the formation of significant numbers of long-lasting, functional human liver cells, with some animals exhibiting levels as high as 20% of donor (human) hepatocytes 11 months after transplantation. A direct correlation was found between hepatocyte activity and phenotype of transplanted cells, cell dose administered, source of cells used on a cell-per-cell basis (bone marrow, cord blood, mobilized peripheral blood), and time after transplantation. Human hepatocytes generated in this model retained functional properties of normal hepatocytes, constituted hepatic functional units with the presence of human endothelial and biliary duct cells, and secreted human albumin that was detected in circulation. Transplanting populations of hematopoietic stem cells can efficiently generate significant numbers of functional hepatic cells in this noninjury large animal model and thus could be a means of ameliorating or curing genetic diseases in which a deficiency of liver cells or their products threatens the life of the fetus or newborn.

APA, Harvard, Vancouver, ISO, and other styles

42

Overi, Diletta, Guido Carpino, Vincenzo Cardinale, Antonio Franchitto, Samira Safarikia, Paolo Onori, Domenico Alvaro, and Eugenio Gaudio. "Contribution of Resident Stem Cells to Liver and Biliary Tree Regeneration in Human Diseases." International Journal of Molecular Sciences 19, no. 10 (September 25, 2018): 2917. http://dx.doi.org/10.3390/ijms19102917.

Full text

Abstract:

Two distinct stem/progenitor cell populations of biliary origin have been identified in the adult liver and biliary tree. Hepatic Stem/progenitor Cells (HpSCs) are bipotent progenitor cells located within the canals of Hering and can be differentiated into mature hepatocytes and cholangiocytes; Biliary Tree Stem/progenitor Cells (BTSCs) are multipotent stem cells located within the peribiliary glands of large intrahepatic and extrahepatic bile ducts and able to differentiate into hepatic and pancreatic lineages. HpSCs and BTSCs are endowed in a specialized niche constituted by supporting cells and extracellular matrix compounds. The actual contribution of these stem cell niches to liver and biliary tree homeostatic regeneration is marginal; this is due to the high replicative capabilities and plasticity of mature parenchymal cells (i.e., hepatocytes and cholangiocytes). However, the study of human liver and biliary diseases disclosed how these stem cell niches are involved in the regenerative response after extensive and/or chronic injuries, with the activation of specific signaling pathways. The present review summarizes the contribution of stem/progenitor cell niches in human liver diseases, underlining mechanisms of activation and clinical implications, including fibrogenesis and disease progression.

APA, Harvard, Vancouver, ISO, and other styles

43

Gallacher, Lisa, Barbara Murdoch, Dongmei Wu, Francis Karanu, Fraser Fellows, and Mickie Bhatia. "Identification of novel circulating human embryonic blood stem cells." Blood 96, no. 5 (September 1, 2000): 1740–47. http://dx.doi.org/10.1182/blood.v96.5.1740.

Full text

Abstract:

Abstract Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 × 105, illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized–peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. Taken together, these studies demonstrate the existence of unique circulating stem cells in early human embryonic development that provide a novel and previously unexplored source of pluripotent stem cell targets for cellular and gene-based fetal therapies.

APA, Harvard, Vancouver, ISO, and other styles

44

Gallacher, Lisa, Barbara Murdoch, Dongmei Wu, Francis Karanu, Fraser Fellows, and Mickie Bhatia. "Identification of novel circulating human embryonic blood stem cells." Blood 96, no. 5 (September 1, 2000): 1740–47. http://dx.doi.org/10.1182/blood.v96.5.1740.h8001740_1740_1747.

Full text

Abstract:

Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 × 105, illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized–peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. Taken together, these studies demonstrate the existence of unique circulating stem cells in early human embryonic development that provide a novel and previously unexplored source of pluripotent stem cell targets for cellular and gene-based fetal therapies.

APA, Harvard, Vancouver, ISO, and other styles

45

Nonome, Kazunobu, Xiao-Kang Li, Terumi Takahara, Yusuke Kitazawa, Naoko Funeshima, Yutaka Yata, Feng Xue, et al. "Human umbilical cord blood-derived cells differentiate into hepatocyte-like cells in the Fas-mediated liver injury model." American Journal of Physiology-Gastrointestinal and Liver Physiology 289, no. 6 (December 2005): G1091—G1099. http://dx.doi.org/10.1152/ajpgi.00049.2005.

Full text

Abstract:

Human umbilical cord blood (HUCB) contains stem/progenitor cells, which can differentiate into a variety of cell types. In this study, we investigated whether HUCB cells differentiate into hepatocytes in vitro and in vivo. We also examined whether CD34 could be the selection marker of stem cells for hepatocytes. HUCB cells were obtained from normal full-term deliveries, and CD34+/−cells were further separated. For in vitro study, HUCB cells were cultured for 4 wk, and expressions of liver-specific genes were examined. For the in vivo study, nonobese diabetic/severe combined immunodeficient mice were subjected to liver injury by a Fas ligand-carried adenoviral vector or only radiated. Mice were treated simultaneously with or without cell transplantation of HUCB, CD34+, or CD34−cells. After 4 wk, human-specific gene/protein expression was examined. In the in vitro study, human liver-specific genes were positive after 7 days of culture. The immunofluorescent study showed positive staining of α-fetoprotein, cytokeratin 19, and albumin in round-shaped cells. In the in vivo study, immunohistochemical analysis showed human albumin-positive, hepatocyte-specific antigen-positive cells in mouse livers of the Fas ligand/transplantation group. Fluorescence in situ hybridization analysis using the human Y chromosome also showed positive signals. However, no difference between transplanted cell types was detected. In contrast, immunopositive cells were not detected in the irradiated/transplantation group. The RT-PCR result also showed human hepatocyte-specific gene expressions only in the Fas ligand/transplantation group. HUCB cells differentiated into hepatocyte-like cells in the mouse liver, and liver injury was essential during this process. The differences between CD34+and CD34−cells were not observed in human hepatocyte-specific expression.

APA, Harvard, Vancouver, ISO, and other styles

46

Plum, J., M. De Smedt, MP Defresne, G. Leclercq, and B. Vandekerckhove. "Human CD34+ fetal liver stem cells differentiate to T cells in a mouse thymic microenvironment." Blood 84, no. 5 (September 1, 1994): 1587–93. http://dx.doi.org/10.1182/blood.v84.5.1587.bloodjournal8451587.

Full text

Abstract:

Hematopoietic stem cells differentiate in the thymus to T cells along precisely defined intermediates. This process is thymic epithelium dependent and involves cytokines and cell-cell interactions between thymic stroma and T-cell precursors. Here we report that highly purified human CD34++ fetal liver stem cells differentiate to mature T cells, when seeded into isolated fetal thymic lobes of severe combined immunodeficient mice, and subsequently cultured in vitro. The human stem cells differentiate sequentially into CD4+CD8-CD3-, CD4+CD8+CD3-, CD4+CD8+CD3+, and finally, CD4+CD8-CD3+4 and CD4-CD8+CD3++ cells. Phenotypic analysis for additional maturation markers showed that these CD4 and CD8 single-positive thymocytes are fully maturate cells. By immunochemistry, human HLA-DR+ cells with a dendritic morphology could be detected. This novel chimeric human-mouse fetal thymus organ culture offers a tool to study human T-cell ontogeny in vitro and is a rapid and reliable test method for T-cell precursor activity of cultured or transfected human stem cells.

APA, Harvard, Vancouver, ISO, and other styles

47

Cesselli, Daniela, Antonio Paolo Beltrami, Alessandra Poz, Stefania Marzinotto, Elisa Comisso, Natascha Bergamin, Evgenia Bourkoula, et al. "Role of Tumor Associated Fibroblasts in Human Liver Regeneration, Cirrhosis, and Cancer." International Journal of Hepatology 2011 (2011): 1–15. http://dx.doi.org/10.4061/2011/120925.

Full text

Abstract:

Tumor associated fibroblasts (TAFs) are considered a microenvironmental element critical for tumor growth and progression. Experimental studies suggest that their origin could be from mesenchymal stem cells (MSCs) derived from the bone marrow. However, the role played by TAFs in cirrhosis, hepatocellular carcinoma development, and progression is largely unknown, andin vitrohuman models are missing. This paper for the first time demonstrates that (1) human neoplastic livers possess a population of multipotent adult stem cells (MASCs) with properties of TAFs; (2) a population of MASC-derived TAFs is already present in cirrhotic, not yet neoplastic, livers; (3) MASCs isolated from nonneoplastic and noncirrhotic liver scan acquire a TAF phenotype when grown in a medium conditioned by tumor cell lines, supporting the notion that TAF could originate from resident primitive cells (MASCs), possibly through a paracrine mechanism.

APA, Harvard, Vancouver, ISO, and other styles

48

Dianat, Noushin, Clara Steichen, Ludovic Vallier, Anne Weber, and Anne Dubart-Kupperschmitt. "Human Pluripotent Stem Cells for Modelling Human Liver Diseases and Cell Therapy." Current Gene Therapy 13, no. 2 (March 1, 2013): 120–32. http://dx.doi.org/10.2174/1566523211313020006.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Ziedan, Mohamed, Maha Ayman, and Dina Mohamed. "The Role of Bone Marrow Mesenchymal Stem Cells and Adipose Tissue-Derived Stem Cells in the Treatment of Liver Failure: A Literature Review." International Journal of Advanced Health Science and Technology 2, no. 2 (March 26, 2022): 115–21. http://dx.doi.org/10.35882/ijahst.v2i2.11.

Full text

Abstract:

Liver disease is a major health problem that endangers human health worldwide. Stem cells have the unique ability to morph or differentiate into different types of cells within the body. In this way, stem cells can be used to seek out damaged liver tissue and regenerate the organ itself. Mesenchymal stem cells are multipotent stem cells that can self-renew and differentiate into different cell types. In other words, mesenchymal stem cells can become a variety of different cell types including adipose tissue, cartilage, muscle, tendon/ligament, bone, neurons, and hepatocytes. Many studies have shown that Mesenchymal stem cells play an essential role in liver recovery, and further research has verified the preliminary effectiveness and safety of these therapies. types of liver disease that are most suitable for MSC application should be determined, and the preparation and engraftment of MSCs should be standardized. Stem cell-based therapies will emerge as an effective treatment strategy for liver diseases in now and the future. Researchers conduct an examination of articles that are in accordance with the issue to be studied. Articles used in literature review are obtained through the database of international journal providers through PubMed, we investigated six clinical studies and discussed what happened in these clinical studies and the extent of the effectiveness of stem cells in treatment and whether the degree of liver disease had a role in the effectiveness of stem cells, we also discussed the mechanism of stem cells in treatment. One of six articles proved that Zeaxanthin dipalmitate (ZD) could enhance the defensive abilities against adverse stresses of human adipose-derived mesenchymal stem cells, One of six articles proved that infusion of allogeneic bone marrow-derived MSCs improving liver function and decreasing the incidence of severe infections. The rest articles proved that MSCs both Bone Marrow Stem cells (BMSCs) and Adipose Derived Stem Cells (ADSCs) are promising therapeutic agents for the liver fibrosis and cirrhosis treatment. In this review, we suggest that formulating and following treatment, Further studies are needed to determine the related mechanisms to enhance MSC efficacy.

APA, Harvard, Vancouver, ISO, and other styles

50

Plum, J., M. De Smedt, MP Defresne, G. Leclercq, and B. Vandekerckhove. "Human CD34+ fetal liver stem cells differentiate to T cells in a mouse thymic microenvironment." Blood 84, no. 5 (September 1, 1994): 1587–93. http://dx.doi.org/10.1182/blood.v84.5.1587.1587.

Full text

Abstract:

Abstract Hematopoietic stem cells differentiate in the thymus to T cells along precisely defined intermediates. This process is thymic epithelium dependent and involves cytokines and cell-cell interactions between thymic stroma and T-cell precursors. Here we report that highly purified human CD34++ fetal liver stem cells differentiate to mature T cells, when seeded into isolated fetal thymic lobes of severe combined immunodeficient mice, and subsequently cultured in vitro. The human stem cells differentiate sequentially into CD4+CD8-CD3-, CD4+CD8+CD3-, CD4+CD8+CD3+, and finally, CD4+CD8-CD3+4 and CD4-CD8+CD3++ cells. Phenotypic analysis for additional maturation markers showed that these CD4 and CD8 single-positive thymocytes are fully maturate cells. By immunochemistry, human HLA-DR+ cells with a dendritic morphology could be detected. This novel chimeric human-mouse fetal thymus organ culture offers a tool to study human T-cell ontogeny in vitro and is a rapid and reliable test method for T-cell precursor activity of cultured or transfected human stem cells.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Human Liver Stem Cells'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles