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1

Thomas, Sonali, DN Sinha, AK Singh, Deepa Deopa, and Richa Niranjan. "Histogenesis of Human Fetal Spleen." National Journal of Clinical Anatomy 06, no. 01 (January 2017): 01–08. http://dx.doi.org/10.1055/s-0039-1700727.

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Abstract Background and Aims: Spleen is the largest secondary lymphatic organ. It acts as a graveyard for RBCs, is essential for immune responses, performs lymphopoiesis in adults and haemopoiesis in fetuses. The present study was conducted to assess the histogenesis of spleen in human fetuses in view of existing literature. Material and Methods: The study was carried out on 34 formalin preserved human fetuses procured from Dr Sushila Tiwari Government Hospital, Haldwani with due clearance from ethical committee. The 6 pm sections of the spleen were stained with Haematoxylin and Eosin and observed under light microscope. Results: At 14 tol5 weeks, spleen had extensive sinusoids filled with RBCs and few lymphocytes. At 16-18 weeks, trabecular arteries were noticed more towards centre along with extensive haemopoietic cells in the venous sinusoids. By 20th week lymphocytic aggregation had started around arterioles. By 24 weeks periarteriolar lymphatic sheath was clearly observed. At term (37-40 weeks), classical primary lymphoid follicle was present but germinal centers were not observed. Conclusion: During earlier differentiation, spleen symbolizes the function of haemopoietic activities and gradually during subsequent gestation; it establishes its identity as a principle lymphoid tissue.
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2

Baird, M. C., J. H. Hendry, and N. G. Testa. "The Radiosensitivity of Human Haemopoietic Progenitor Cells." International Journal of Radiation Biology 56, no. 5 (January 1989): 617–21. http://dx.doi.org/10.1080/09553008914551831.

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3

SCHOFIELD, Karen P., John T. GALLAGHER, and Guido DAVID. "Expression of proteoglycan core proteins in human bone marrow stroma." Biochemical Journal 343, no. 3 (October 25, 1999): 663–68. http://dx.doi.org/10.1042/bj3430663.

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Heparan sulphate proteoglycans (HSPGs) present on the surface of bone marrow stromal cells and in the extracellular matrix (ECM) have important roles in the control of adhesion and growth of haemopoietic stem and progenitor cells. The two main groups of proteoglycans which contain heparan sulphate chains are members of the syndecan and glypican families. In this study we have identified the main surface membrane and matrix-associated HSPGs present in normal human bone marrow stroma formed in long-term culture. Proteoglycans were extracted from the adherent stromal layers and treated with heparitinase and chondroitinase ABC. The core proteins were detected by Western blotting using antibodies directed against syndecans-1-4, glypican-1 and the ECM HSPG, perlecan. Stromal cell expression at the RNA level was detected by Northern blotting and by reverse transcription PCR. Glypican-1, syndecan-3 and syndecan-4 were the major cell-membrane HSPG species and perlecan was the major ECM proteoglycan. There was no evidence for expression of syndecan-1 protein. Syndecan-3 was expressed mainly as a variant or processed 50-55 kDa core protein and in lower amounts as the characteristic 125 kDa core protein. These results suggest that syndecan-3, syndecan-4 and glypican-1 present on the surface of marrow stromal cells, together with perlecan in the ECM, may be responsible for creating the correct stromal ‘niche’ for the maintenance and development of haemopoietic stem and progenitor cells. The detection of a variant form of syndecan-3 as a major stromal HSPG suggests a specific role for this syndecan in haemopoiesis.
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4

Grainger, John D., Lez J. Fairbairn, and Robert F. Wynn. "Murine Mesenchymal Stem Cells Improve Haemopoietic Engraftment in a Murine Transplant Model and Is Maximised through Osteogenic Stimulation." Blood 104, no. 11 (November 16, 2004): 1183. http://dx.doi.org/10.1182/blood.v104.11.1183.1183.

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Abstract Several studies have preciously shown improved engraftment of human haemopoietic stem cells (HSC) following co-infusion of human mesenchymal stem cells (MSC). However, these studies have been criticised for using xenogeneic recipients which might support human haemopoiesis through the production of species-specific cytokines and growth factors by human MSC. To further investigate the potential for MSC to support HSC engraftment we used a murine to murine transplant model to co-infuse purified murine MSC and murine HSC. The MSC were derived from collagenase-treated bone fragments of the Rosa26 murine strain, had the phenotype CD45- CD31-CD11b- Sca-1bright VCAM1+ and could differentiate into osteocytes, chondrocytes and adipocytes. Donor and recipient HSC were obtained from unmanipulated bone marrow of either the C57Bl/6J murine strain, CD45 isotype CD45.2, or the PEP3b murine strain, expressing CD45.1. Following 10Gy irradiation to the recipients HSC and MSC were co-infused. Donor and recipient haemopoietic engraftment in the peripheral blood was quantified by FACS analysis of the CD45.1/CD45.2 ratio. Successive transplant experiments persistently showed improved donor haemopoietic engraftment following co-infusion of 2 x 105 BM cells and 1 x 106 MSC (three seperate transplant series p=0.001, p=0.09 and p=0.13). The beneficial effect was maximal at the lower HSC dose of 1 x 105 BM cells (p=0.004, p=0.045 and uninterpretable in the third transplant series due to excessive death observed in the non-MSC recipients). Increasing the MSC dose to 2 x 106 cells showed a non-significant increase in survival and donor haemopoietic engraftment but further MSC escalation resulted in fatal emboli post-infusion. LacZ staining of tissue sections failed to show evidence of MSC outside the lungs but was detected at very low levels in the bone from one recipient. As MSC are osteoblast precursors and recent literature suggests a role of osteoblasts as the HSC niche we investigated the effect of pre-culturing our MSC population in osteogenic media prior to transplant. Following 16 days of culture approximately 40% of colonies showed ALP activity. At this time point osteogenic-stimulated MSC (O-MSC) were removed from culture, washed to remove any residual osteogenic media, and infused in our standard method. O-MSC recipients receiving 1 x 105 BM cells showed a mean engraftment of 79% compared to 21% in non-msc recipients receiving 2 x 105 BM cells (p=0.000017), and 42% in recipients receiving standard MSC and 1 x 105 BM cells (p=0.01). In conclusion we confirm improved haemopoietic engraftment in a non-xenogeneic model and does not require significant MSC engraftment. The beneficial effect is maximised through osteogenic stimulation of MSC suggesting the possibility that the mechanism may be through priming of the HSC niche.
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5

Laurent, Monique, Geneviève Clémancey-Marcille, and Daniel Hollard. "Normal and Leukaemic Human Haemopoietic Cells in Diffusion Chamber." Scandinavian Journal of Haematology 24, no. 3 (April 24, 2009): 205–12. http://dx.doi.org/10.1111/j.1600-0609.1980.tb01328.x.

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6

Morgan, Richard, Ruji Begum, Davinder Theti, Mutale Chansa, Ruth Pettengell, and Jastinder Sohal. "HOXA9 expression increases with age in human haemopoietic cells." Leukemia Research 29, no. 10 (October 2005): 1221–22. http://dx.doi.org/10.1016/j.leukres.2005.03.007.

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7

Averett, D. R., H. N. Steinberg, G. W. Koszalka, T. Spector, and T. A. Krenitsky. "Purine Arabinosides as Inhibitors of Human Haemopoietic Progenitor Cells." Antiviral Chemistry and Chemotherapy 3, no. 3 (June 1992): 179–82. http://dx.doi.org/10.1177/095632029200300308.

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Four purine arabinosides that inhibit varicella-zoster virus (VZV) replication in vitro were tested as inhibitors of colony formation by progenitor cells from normal human bone marrow. In general, erythroid burst forming cells (BFU-E) were more sensitive to inhibition by these compounds than were either erythroid colony forming cells (CFU-E) or granulocyte/macrophage colony forming cells (CFU-GM). A 50% reduction in colony formation (IC50) was observed for BFU-E in the presence of 8 μM 6-methoxypurine arabinoside. Adenine arabinoside and hypoxanthine arabinoside had IC50 values of 1 μM and 4 μM respectively, whereas 6-ethoxypurine arabinoside was not inhibitory (IC50 > 50 μM). Enzyme studies showed that both 6-methoxypurine arabinoside and adenine arabinoside were converted to hypoxanthine arabinoside by adenosine deaminase. 6-Ethoxypurine arabinoside was a much less efficient substrate. When the BFU-E assays were performed in the presence of an inhibitor of adenosine deaminase, 6-methoxypurine arabinoside became non-inhibitory. In contrast, adenine arabinoside became much more inhibitory (IC50 = 0.03 μM). The potency of hypoxanthine arabinoside was unaffected. Thus, incubation of 6-methoxypurine arabinoside and adenine arabinoside under conditions appropriate for the BFU-E assay resulted in the in situ conversion of these compounds to hypoxanthine arabinoside. Biotransformation of compounds must be considered in the assessment of toxicity in vitro.
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8

Kotsianidis, Ioannis, Scott Patterson, Marianna Politou, Antonio Almeida, Despoina Pantelidou, Costas Tsatalas, George Bourikas, Irene Roberts, and Anastasios Karadimitris. "Evidence That Human NKT Cells Enhance Haemopoiesis through Recognition of CD1d Expressed in Haemopoietic Stem Cells with Long Term Clonogenic Capacity." Blood 104, no. 11 (November 16, 2004): 4129. http://dx.doi.org/10.1182/blood.v104.11.4129.4129.

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Abstract NKT cells, a novel class of regulatory T cells, secrete haemopoietic cytokines (GM-CSF, IL-3, IL-6) upon engagement of their TCR. Because of this property we hypothesized that NKT cells are involved in the regulation of haemopoiesis. NKT cells constitute <0.1% of T cells in blood, bone marrow and cord blood and are restricted by the glycolipid-presenting, non-polymorphic MHC-like molecule CD1d. CD1d is expressed in antigen presenting cells, thymocytes and in a variety of epithelial tissues including keratinocytes and enterocytes, but its expression in haematopoietic stem cells (HSC) has not been studied. Therefore we studied first the expression and function of CD1d in haemopoietic stem cells. Using multi-colour flow cytometry, we show that 1% of MACS-selected cord blood CD34+ cells are CD1d+ (n=6, range 0.4–1.67%). CD1d+CD34+ HSC express a variety of surface markers indicative of primitive HSC: CD7: 36.1% (35.6–36.4%), CD133: 68% (46.2–81.54%), CD117:74.2% (51–85.5%) and CD90 (Thy-1): 32.3% (26.7–39.1%); moreover, 6,2% (1.9–10.5%) and 12,8% (10.1–16%) of CD1d+CD34+ are CD1d+CD34+HLADR− and CD1d+CD34+CD38− respectively, consistent with an immature HSC phenotype. Expression of these markers by CD1d−CD34+ were identical to CD1d+CD34+ cells. Consistent with this, in long-term colony initiating cell (LTC-IC) assays (n=4), highly purified, flow-sorted, lineage-depleted (Stem Cell Technologies) Lin-CD1d+CD34+ HSC displayed a LTC-IC frequency of 1 in 35.7 cells (range 24.4–38) equivalent to those of CD1d−CD34+ HSC: LTC-IC frequency of 1 in 25.4 cells (range 20–30.3). Short term CFC activity of Lin−CD34+CD1d+ is slightly lower than their Lin−CD1d−CD34+ counterparts: 1 CFC per 15.3 cells (7.7–37.7) versus 1 CFC per 4.2 cells (3.8–5), respectively. To investigate the effect of cord blood NKT cells on the CFC activity of CD34+ cells, NKT were first activated ex vivo for 10 days in the presence of the CD1d-presented glycolipid a-galactosylceramide and subsequently were purified by flow-sorting using mAbs specific to their TCR a and b chains, i.e., anti-TCR Va24 and Vb11. Purified NKT were co-cultured in a ratio of 10:1 with CD34+ cells. In the absence of exogenous cytokines NKT enhanced the clonogenic capacity of CD34+ cells by 3-fold: 1 CFC per 14 cells (range 10.4–21) in the presence of NKT vs 1 per 43 cells (range 37–55.5) in the absence of NKT (n=4; p=0.024). By contrast, activated or resting autologous T cells co-cultured with CD34+ cells at the same ratio (10:1) had no effect on the CFC frequency, indicating that this enhancing effect on haemopoiesis is a unique property of NKT cells. The effect of NKT in the long-term clonogenic capacity is currently being evaluated. In summary, we have shown that a) CD1d is a novel marker expressed in HSC with long- and short -term clonogenic ability and b) CD1d-restricted NKT cells promote haemopoiesis These findings reveal a novel link between haemopoiesis and the CD1d-NKT axis of immune regulation and set the scene for the study of the role of NKT cells in the processes of engraftment and rejection in HSC transplantation.
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9

Easterbrook, Jennifer, Lesley Forrester, and Alexander Medvinsky. "Differentiation of haemopoietic stem cells and progenitor cells from human pluripotent stem cells." Lancet 387 (February 2016): S39. http://dx.doi.org/10.1016/s0140-6736(16)00426-8.

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10

Cicuttini, F. M., M. Loudovaris, and A. W. Boyd. "Interactions between purified human cord blood haemopoietic progenitor cells and accessory cells." British Journal of Haematology 84, no. 3 (July 1993): 365–73. http://dx.doi.org/10.1111/j.1365-2141.1993.tb03088.x.

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11

DIFALCO, Marcos R., and L. Fernando CONGOTE. "Preparation of a recombinant chimaera of insulin-like growth factor II and interleukin 3 with high proliferative potency for haemopoietic cells." Biochemical Journal 326, no. 2 (September 1, 1997): 407–13. http://dx.doi.org/10.1042/bj3260407.

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We have found that a slightly modified insulin-like growth factor II (IGF II) consisting of a chimaera of bombyxin and human IGF II (BOMIGF) is properly secreted in insect cells by using the baculovirus expression system. Human interleukin 3 (IL-3) was attached to the C-terminal amino acid residue of BOMIGF with peptide linkers containing five or twelve residues. Only the chimaera with the 12-residue linker had biological activities of both IGF II and IL-3. The chimaera had a significantly higher mitogenic activity than IL-3 in cell cultures of the human haemopoietic cell line TF-1 and its effect could be observed even at femtomolar concentrations. It was also able to stimulate thymidine incorporation in IGF II-dependent bovine fetal erythroid cells. The chimaera significantly increased the number of macroscopic haemopoietic colonies in cultures of human peripheral blood in comparison with IL-3 or mixtures of IL-3 and BOMIGF in vitro. Subcutaneous injection of a BOMIGF–mouse IL-3 chimaera in normal C57BL/6 mice resulted in a significant increase of the number of spleen stem cells producing macroscopic haemopoietic colonies. This new system for the biosynthesis of IGF–cytokine fusion proteins in insect cells might prove advantageous for the low-cost and high-yield production of molecules with complementary or synergistic biological activities.
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12

Moretti, Paul, Paul Simmons, Paul Thomas, David Haylock, Peter Rathjen, Mathew Vadas, and Richard D'Andrea. "Identification of homeobox genes expressed in human haemopoietic progenitor cells." Gene 144, no. 2 (July 1994): 213–19. http://dx.doi.org/10.1016/0378-1119(94)90380-8.

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13

Van Den Heuvel, R. L., G. Schoeters, and H. Leppens. "Haematotoxicity testing in vitro using human cord blood haemopoietic cells." Toxicology in Vitro 11, no. 5 (October 1997): 689–93. http://dx.doi.org/10.1016/s0887-2333(97)00049-0.

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14

Biasco, Luca, Cristina Baricordi, Stefania Merella, Cynthia Bartholomae, Alessandro Ambrosi, Danilo Pellin, Clelia Di Serio, Christof Von Kalle, Manfred Schmidt, and Alessandro Aiuti. "Uncovering Haematopoietic System Dynamics and Single Multipotent Progenitors Activity In Vivo In Humans by Retroviral Tagging." Blood 116, no. 21 (November 19, 2010): 2611. http://dx.doi.org/10.1182/blood.v116.21.2611.2611.

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Abstract Abstract 2611 The long-standing model of human haematopoiesis postulates that myeloid and lymphoid lineages branch separately at very early stages, producing myeloid or erythroid cells and T or B cells, respectively. Conversely, a revised scheme of haematopoietic hierarchy was recently proposed, in which myeloid cells represent a prototype of blood cells, while erythroid, T and B cells are specialized cell types. The validity of these models has been mainly tested in vivo in the mouse, and in vitro through clonal assays on human haemopoietic stem cells (HSC). However, a clear definitive elucidation of the real nature of human haemopoiesis should ideally involve the ability to track the dynamics, survival and differentiation potential of haemopoietic progenitor clones for a long period of time directly in vivo in humans. Upon retroviral gene transfer, transduced cells are univocally tagged by vector insertions allowing them to be distinguished and tracked in vivo by integration profiling. We previously showed that gene therapy (GT) for adenosine deaminase (ADA) deficient SCID based on infusion of transduced CD34+ cells and reduced intensity conditioning, resulted in full multilineage engraftment, in the absence of aberrant expansions. Therefore, long-term studies in these patients provide a unique human model to study in depth haemopoietic clonal dynamics by retroviral tagging. For this reason, we performed a comprehensive multilineage longitudinal insertion profile of bone marrow (BM) (CD34+, CD15+, CD19+, Glycophorin+) and peripheral blood (PB) (CD15+, CD19+, CD4+, CD8+ cells, naïve and memory T cell subpopulations) cells in 4 patients 3–6 years after GT, retrieving to date 1055 and 1999 insertions from BM and PB cell lineages respectively. We could shape the insertional landscape of each lineage through a tri-factorial analysis based on the number of integrations retrieved, the percentage of vector positive cells and the number of insertion shared with other lineages. We were able to uncover the effects of selective advantages of gene-corrected cells in periphery and the frequency of identical integrants in different haematopoietic compartments. BM cells displayed the highest proportion of shared integrants (up to 58.1%), reflecting the real-time repopulating activity of gene-corrected progenitors. On the other hand, PB samples carried in general a higher frequency of vector positive cells, with the exception of PB CD15+ cells showing insertional landscapes very similar to the one of BM lineages. Interestingly, the detection of exclusively shared myeloid-T\B or myeloid-erythroid integrants may be supportive of a myeloid-based haemopoiesis model. We also uncovered “core integrants”, shared between CD34+ cells and both lymphoid and myeloid lineages, stably tagging active long-term multipotent progenitors overtime. Strikingly, one of these progenitor clones carried an insertion inside one of the two fragile sites of MLLT3 gene, involved by translocation events in mixed lineage leukemia. We were able to track this and another integrant (downstream the LRRC30 gene) by specific PCRs, confirming the multilineage contribution to haematopoiesis of the relative progenitor clones and their fluctuating lineage outputs over 4 years, without showing aberrant expansions. We also retrieved 170 and 174 integrations from 4 T cell subtypes (Naive, TEMRA, Central and Effector memory) in two patients under PBL-GT and HSC-GT respectively. We found evidences that single naive T cell clones may survive in patients for up to 10 years after last infusion while maintaining their differentiation capacity into different T cell subpopulations. Interestingly, a cluster of 4 insertions (one of them shared among all T cell subtypes) was found in proximity of the interferon regulatory factor 2 binding protein 2 (IRF2BP2) gene in naive T cells from PBL-GT patient, thus suggesting an influence of transcriptional activity of this region on selective advantage of gene-corrected lymphocytes. In conclusion, through retroviral tagging, we can uniquely track single transduced haemopoietic cells directly in vivo in humans. The application of mathematical models to our insertion datasets is allowing to uncover new information on the fate and activity of haematopoietic progenitors and their differentiated progeny years after transplantation in GT patients. Disclosures: No relevant conflicts of interest to declare.
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15

Nicola, Nicos A. "Donald Metcalf AC. 26 February 1929 — 15 December 2014." Biographical Memoirs of Fellows of the Royal Society 62 (January 2016): 409–31. http://dx.doi.org/10.1098/rsbm.2016.0013.

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Donald Metcalf was one of Australia's most distinguished medical researchers and is acknowledged internationally as the father of the modern field of haemopoietic growth factors. He defined the hierarchy of haemopoietic progenitor cells, purified and cloned the major molecular regulators of their growth and maturation, determined their mechanisms of action and participated in their development for clinical use in cancer patients. He received numerous awards and distinctions during his career, but was most pleased by the fact that his life's work improved human health.
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16

Nicola, Nicos A. "Donald Metcalf 1929–2014." Historical Records of Australian Science 27, no. 2 (2016): 176. http://dx.doi.org/10.1071/hr16003.

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Donald Metcalf was one of Australia's most distinguished medical researchers and is acknowledged internationally as the father of the modern field of haemopoietic growth factors. He defined the hierarchy of haemopoietic progenitor cells, purified and cloned the major molecular regulators of their growth and maturation, determined their mechanisms of action and participated in their development for clinical use in cancer patients. He received numerous awards and distinctions during his career, but was most pleased by the fact that his life's work improved human health.
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17

BACCARANI, MICHELE, and SVEN-AAGE KILLMANN. "Evidence against Human Bone Marrow Lymphocytes being Committed Haemopoietic Stem Cells." Scandinavian Journal of Haematology 9, no. 1-6 (April 24, 2009): 339–42. http://dx.doi.org/10.1111/j.1600-0609.1972.tb00950.x.

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18

Roberts, Pamela J., Elahe Mollapour, Michael J. Watts, and David C. Linch. "Activation of phospholipase A2 during differentiation of human haemopoietic progenitor cells." Biochemical Society Transactions 26, no. 3 (August 1, 1998): S233. http://dx.doi.org/10.1042/bst026s233.

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19

MILOSEVITS, J., E. POCSIK, B. SCHMIDT, P. REMENYI, Z. S. INTODI, M. RETI, A. BATAI, et al. "Immunophenotypic and Functional Characteristics of Haemopoietic Cells from Human Cord Blood." Scandinavian Journal of Immunology 42, no. 4 (October 1995): 493–500. http://dx.doi.org/10.1111/j.1365-3083.1995.tb03685.x.

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20

El-Masry, Manal, Heba Gouda, Rania Fawzy, and Nihal Salah El-Din. "Differentiation of insulin-producing cells from human cord bloodderived haemopoietic stem cells in vitro." Comparative Clinical Pathology 21, no. 6 (November 9, 2011): 1707–11. http://dx.doi.org/10.1007/s00580-011-1353-x.

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21

Morris, A. J., J. E. Turnbull, G. P. Riley, M. Y. Gordon, and J. T. Gallagher. "Production of heparan sulphate proteoglycans by human bone marrow stromal cells." Journal of Cell Science 99, no. 1 (May 1, 1991): 149–56. http://dx.doi.org/10.1242/jcs.99.1.149.

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Haemopoietic progenitors from human bone marrow bind strongly to human marrow stromal cell cultures but the interaction only occurs if the stromal cells are maintained in methyl prednisolone. Heparan sulphate has been implicated in this interaction and in the binding of haemopoietic cell growth factors. In the present study we have compared the molecular structures of the heparan sulphate proteoglycans, metabolically labelled with [35S]sulphate, produced by methyl prednisolone-treated and untreated human marrow stromal cells in vitro. [35S]proteoglycans were examined in the cell layers (extracted with 1% (v/v) Triton X-100 in 6 M urea) and in the culture medium. Fractionation of proteoglycans by ion-exchange chromatography indicated that the heparan sulphate produced by the treated cultures eluted at a higher NaCl concentration than the counterpart from untreated cells. The heparan sulphate appeared to be mainly expressed on the cell surface, since it was efficiently extracted by treatment with dilute trypsin (50 micrograms ml-1 for 10 min). All cultures contained two heparan sulphate proteoglycan species, the major component eluted from a Sepharose CL-4B column with a median Kav of 0.33 and apparently contained an average of only one heparan sulphate chain. Small quantities of a larger proteoglycan, which was eluted in the void volume from the CL-4B column, was also detected, mainly in the cell layer extracts. The molecular structure of the heparan sulphate chains was analysed by oligosaccharide mapping, following specific enzymic depolymerisation, and separation of breakdown products by gradient PAGE. The maps revealed significant differences in overall enzyme susceptibilities and sulphation patterns of polysaccharides produced by methyl prednisolone-treated and untreated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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22

Zandstra, Conneally, Piret, and Eaves. "Ontogeny‐associated changes in the cytokine responses of primitive human haemopoietic cells." British Journal of Haematology 101, no. 4 (June 1998): 770–78. http://dx.doi.org/10.1046/j.1365-2141.1998.00777.x.

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23

Turner, Curtis W., David R. Archer, John Wong, Andrew M. Yeager, and William H. Fleming. "In utero transplantation of human fetal haemopoietic cells in NOD/SCID mice." British Journal of Haematology 103, no. 2 (November 1998): 326–34. http://dx.doi.org/10.1046/j.1365-2141.1998.01003.x.

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24

Craig, William, Sibrand Poppema, Marie-Terese Little, Wieslawa Dragowska, and Peter M. Lansdorp. "CD45 isoform expression on human haemopoietic cells at different stages of development." British Journal of Haematology 88, no. 1 (September 1994): 24–30. http://dx.doi.org/10.1111/j.1365-2141.1994.tb04972.x.

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25

Krüger, W., R. Lohner, R. Jung, N. Kröger, and A. R. Zander. "Expression of human milk fat globulin proteins in cells of haemopoietic origin." British Journal of Cancer 83, no. 7 (October 2000): 874–79. http://dx.doi.org/10.1054/bjoc.2000.1404.

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26

Bains, M. A., T. G. Hoy, P. Baines, and A. Jacobs. "Nuclear c-myc protein, maturation, and cell-cycle status of human haemopoietic cells." British Journal of Haematology 67, no. 3 (November 1987): 293–300. http://dx.doi.org/10.1111/j.1365-2141.1987.tb02350.x.

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27

Morey, Adrienne L., and Kenneth A. Fleming. "Immunophenotyping of fetal haemopoietic cells permissive for human parvovirus B19 replication in vitro." British Journal of Haematology 82, no. 2 (October 1992): 302–9. http://dx.doi.org/10.1111/j.1365-2141.1992.tb06422.x.

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28

Watt, S. M., and J. W. M. Visser. "Recent advances in the growth and isolation of primitive human haemopoietic progenitor cells." Cell Proliferation 25, no. 4 (July 1992): 263–97. http://dx.doi.org/10.1111/j.1365-2184.1992.tb01440.x.

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29

Bertolini, Francesco, Lucia De Monte, Chiara Corsini, Lorenza Lazzari, Eleonora Lauri, Davide Soligo, Maureen Ward, Arthur Bank, and Fabio Malavasi. "Retrovirus-mediated transfer of the multidrug resistance gene into human haemopoietic progenitor cells." British Journal of Haematology 88, no. 2 (October 1994): 318–24. http://dx.doi.org/10.1111/j.1365-2141.1994.tb05025.x.

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30

Doody, G. M., J. P. Leek, A. K. Bali, A. Ensser, A. F. Markham, and E. A. de Wynter. "Marker gene transfer into human haemopoietic cells using a herpesvirus saimiri-based vector." Gene Therapy 12, no. 4 (December 23, 2004): 373–79. http://dx.doi.org/10.1038/sj.gt.3302422.

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31

Lopez, Angel F., Michael J. Elliott, Joanna Woodcock, and Mathew A. Vadas. "GM-CSF, IL-3 and IL-5: cross-competition on human haemopoietic cells." Immunology Today 13, no. 12 (January 1992): 495–500. http://dx.doi.org/10.1016/0167-5699(92)90025-3.

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32

Lamy, Isabelle, Anne Corlu, Olivier Fardel, Virginie Gandemer, Mickael Rialland, Claudine Leberre, Pierre‐Yves Le Prise, Renee Fauchet, Laure Coulombel, and Christiane Guguen‐Guillouzo. "Rat liver biliary epithelial cells support long‐term production of haemopoietic progenitors from human CD34 + cells." British Journal of Haematology 98, no. 3 (September 1997): 560–68. http://dx.doi.org/10.1046/j.1365-2141.1997.2813098.x.

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33

Introna, Martino, Anna Maria Barbui, JosÉE Golay, Federica Bambacioni, Raffaella SchirÒ, Sergio Bernasconi, Ferruccio Breviario, et al. "Rapid retroviral infection of human haemopoietic cells of different lineages: efficient transfer in fresh T cells." British Journal of Haematology 103, no. 2 (November 1998): 449–61. http://dx.doi.org/10.1046/j.1365-2141.1998.01020.x.

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34

Gotoh, Akihiko, Suzanna Reid, Keisuke Miyazawa, and Hal E. Broxmeyer. "SDF-1 suppresses cytokine-induced adhesion of human haemopoietic progenitor cells to immobilized fibronectin." British Journal of Haematology 106, no. 1 (July 1999): 171–74. http://dx.doi.org/10.1046/j.1365-2141.1999.01517.x.

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35

Cork, Michael J., Andrew C. Riches, and Eric G. Wright. "A stimulator of murine haemopoietic stem cell proliferation produced by human fetal liver cells." British Journal of Haematology 63, no. 4 (August 1986): 775–83. http://dx.doi.org/10.1111/j.1365-2141.1986.tb07561.x.

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36

Strobl, Herbert, Masafumi Takimoto, Otto Majdic, Paul Höcker, and Walter Knapp. "Antigenic analysis of human haemopoietic progenitor cells expressing the growth factor receptor c-kit." British Journal of Haematology 82, no. 2 (October 1992): 287–94. http://dx.doi.org/10.1111/j.1365-2141.1992.tb06420.x.

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37

Eridani, Sandro, Umberto Mazza, Paolo Massaro, Maria Luisa La Targia, Anna Teresa Maiolo, and Andrea Mosca. "Cytokine effect on ex vivo expansion of haemopoietic stem cells from different human sources." Biotherapy 10, no. 4 (December 1998): 295–98. http://dx.doi.org/10.1007/bf02678549.

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38

Xi, XIAODONG, NICOLE SCHLEGEL, JACQUES P. CAEN, ADRIAN MINTY, SYLVIE FOURNIER, DANIEL CAPUT, PASCUAL FERRARA, and ZHONG C. HAN. "Differential effects of recombinant human interleukin-13 on the in vitro growth of human haemopoietic progenitor cells." British Journal of Haematology 90, no. 4 (August 1995): 921–27. http://dx.doi.org/10.1111/j.1365-2141.1995.tb05216.x.

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39

Hart, D. N., and J. L. McKenzie. "Isolation and characterization of human tonsil dendritic cells." Journal of Experimental Medicine 168, no. 1 (July 1, 1988): 157–70. http://dx.doi.org/10.1084/jem.168.1.157.

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Анотація:
Human dendritic cells were isolated from tonsils by density gradient separation followed by FACS IV sorting with mAbs to remove contaminating cell populations. The resulting dendritic cell population consisted of large cells with plentiful basophilic cytoplasm, lacking in granules but containing a prominent Golgi apparatus and numerous mitochondria. The cell membrane was irregular, and marked cell protrusions were obvious when stained with anti-HLA class II reagents. Their nuclei were irregular and often indented with a visible nucleolus. These cells were not phagocytic and stimulated autologous and allogeneic lymphocytes more effectively than other tonsil cell types in MLR. Phenotypic analysis of these cells confirmed that they expressed the leucocyte common antigen and stained strongly for HLA-class II antigens. Tonsil dendritic cells also coexpressed the LFA-1 alpha and LFA-1 beta chains but did not stain with a wide variety of anti-monocyte or anti-macrophage antibodies. The cells also lacked Fc and complement receptors and failed to stain with CD1 antibodies. Extensive testing with mAbs revealed only a few positive reactions, and these were consistent with reports of these antibodies staining interdigitating cells in tissue sections. This established that tonsil dendritic cells belong to the unique haemopoietic cell lineage of dendritic cells. No cytoplasmic staining of IL-1 alpha or IL-1 beta was demonstrated, although these lymphokines were readily detected in activated monocytes.
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40

Avent, N., P. A. Judson, S. F. Parsons, G. Mallinson, D. J. Anstee, M. J. A. Tanner, P. R. Evans, E. Hodges, A. G. Maciver, and C. Holmes. "Monoclonal antibodies that recognize different membrane proteins that are deficient in Rhnull human erythrocytes. One group of antibodies reacts with a variety of cells and tissues whereas the other group is erythroid-specific." Biochemical Journal 251, no. 2 (April 15, 1988): 499–505. http://dx.doi.org/10.1042/bj2510499.

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Анотація:
1. Rhnull human erythrocytes lack all of the antigens of the Rh and LW blood group systems and have abnormal shape and an increased osmotic fragility. In this paper two murine monoclonal antibodies raised against intact human erythrocytes were used to investigate further the abnormalities in these cells. BRIC 125 reacts weakly with Rhnull erythrocytes and BRIC 69 does not react at all. The results showed that BRIC 125 reacts with a component of Mr 47,000-52,000 which has a substantial content of N-glycans. In contrast, BRIC 69 reacted with a band of Mr 31,000 together with a very diffuse band of Mr 35,000-52,000. Treatment of BRIC 69 immunoprecipitates with endoglycosidase F/peptidyl-N-glycosidase F resulted in the loss of both BRIC 69 reactive components and the appearance of a new band of Mr similar to that of the Rh(D) polypeptide. 2. BRIC 125 had a broad reactivity with cells in peripheral blood, whereas the reactivity of BRIC 69 was confined to erythrocytes. BRIC 125, but not BRIC 69, reacted with human kidney tissue and bound to endothelium in peritubular capillaries, arteries and veins as well as the epithelial tissue of distal tubules. BRIC 125 stained haemopoietic cells, foetal hepatocytes and megakaryocytes in foetal liver and sinusoidal cells, hepatocytes and portal tracts in adult liver. In contrast, BRIC 69 reactivity was confined to haemopoietic cells in foetal liver. The BRIC 125 epitope has a wide tissue distribution, suggesting the occurrence of a related group of polypeptides which have a general functional role on cell surfaces. 3. Rhnull erythrocytes are deficient in at least four different membrane polypeptides.
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41

Bunce, C. M., P. J. French, P. Allen, J. C. Mountford, B. Moor, M. F. Greaves, R. H. Michell, and G. Brown. "Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts." Biochemical Journal 289, no. 3 (February 1, 1993): 667–73. http://dx.doi.org/10.1042/bj2890667.

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We have compared the levels of inositol metabolites in three pairs of normal and transformed cells which have been matched with respect to their cell lineage, differentiation and proliferation status: (i) normal human myeloid blast cells and the human promyelocytic leukaemic cell line, HL60; (ii) human umbilical-cord T-helper cells and C8166 cells, a HTLV-1-transformed T-helper cell line; and (iii) an interleukin 3-dependent long-term culture of murine pro-B-cells (BAF3) and BAF3 cells transformed by transfection with the bcr-abl oncogene. Complex patterns of inositol metabolites were present in each of the cell populations. Although there were a number of differences in the levels of certain inositol metabolites between individual cell populations in the paired groups, we did not observe any consistent difference in the levels of inositol metabolites between the proliferating normal and transformed cells. In particular, our data do not support the reported correlation between elevated glycerophosphoinositol (GroPIns) levels and transformation of cells by membrane and cytoplasmic oncogenes which has been reported by other workers. All the cells contained high concentrations of Ins(1,3,4,5,6)P5 (between 12 and 55 microM) and InsP6 (between 37 and 105 microM). The HTLV1-transformed T-helper cells had particularly high levels of total inositol phosphates (predominantly GroPIns, an unidentified inositol bisphosphate and InsP6). The observations are discussed with reference to cell transformation and to the differentiation status of the paired populations.
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42

Lyon, Mary F. "Charles Edmund Ford. 24 October 1912 – 7 January 1999." Biographical Memoirs of Fellows of the Royal Society 47 (January 2001): 189–201. http://dx.doi.org/10.1098/rsbm.2001.0011.

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Анотація:
Charles Edmund Ford was distinguished for his outstanding contributions to mammalian cytogenetics, particularly human cytogenetics. He was especially renowned for his part in establishing the number of human chromosomes as 46, rather than 48 as previously believed. However, his contributions to the use of chromosome variants as cell markers in tracing cell lineages, particularly of haemopoietic cells, were of equal importance. He had a great mastery of cytological techniques and his ability to devise suitable methods for mammalian cells was a major factor in his contribution to the explosive advance of human and other mammalian genetics in the 1960s. Equally important were his superb observational powers in interpreting chromosome aberrations under the microscope, and his scrupulous adherence to scientific method.
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43

Tohyama, Kaoru, Yumi Tohyama, Takashi Nakayama, Takanorf Ueda, Toru Nakamura, and Yataro Yoshida. "A novel factor-dependent human myelodysplastic cell line, MDS92, contains haemopoietic cells of several lineages." British Journal of Haematology 91, no. 4 (December 1995): 795–99. http://dx.doi.org/10.1111/j.1365-2141.1995.tb05391.x.

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44

Ivanovs, Andrejs, Stanislav Rybtsov, Lindsey Welch, Richard A. Anderson, Marc L. Turner, and Alexander Medvinsky. "Highly potent human haemopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region." Lancet 381 (February 2013): S12. http://dx.doi.org/10.1016/s0140-6736(13)60452-3.

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45

Kalk, Emma, Karen Piper, Guy Pratt, Lawrence Young, Jane Steele, and Paul Moss. "CD8+ T Cell Responses to the Polycomb Protein EZH2 in Patients with Haemopoietic Malignancies." Blood 106, no. 11 (November 16, 2005): 3914. http://dx.doi.org/10.1182/blood.v106.11.3914.3914.

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Анотація:
Abstract Polycomb Group (PcG) genes encode transcriptional repressors that have been implicated in stem cell survival and cell fate determination (Lessard J et al. Blood. 1998). They are the human homologues of the Drosophila Polycomb and Posterior sex comb genes where they maintain segment-specific expression of the homeotic (Hox) genes. Hox gene products are transcription factors involved in cell fate determination and have been implicated in normal haematopoiesis and leukaemic transformation. In mammals, the PcG genes are highly conserved and essential for normal embryonal development and cell cycle control, as well as the regulation of haematopoiesis. Two distinct PcG gene subsets have been identified which demonstrate consistent and often mutually exclusive expression in haemopoietic cells, the patterns correlating with phenotypically distinct populations in the lymph nodes and thymus. BMI-1 and EZH2 are representative examples of these two subsets of PcG genes. BMI-1 expression is essential for stem cell self-renewal whereas EZH2 is required for cell proliferation. Disrupted expression of both of these genes has been demonstrated in a range of haemopoietic and non-haemopoietic malignancies and appears to deliver a proliferative advantage to the cell. Humoral and T cell immunity to BMI-1 and EZH2 has been observed in patients with hepatocellular and prostate carcinoma, suggesting that these proteins may act as tumour antigens. However, CD8+ T cell responses to peptides derived from the proteins have also been demonstrated in healthy controls indicating that T cell tolerance might not be complete. Using the cytokine secretion assay and HLA-tetramer staining, HLA A*0201-restricted CD8+ T cell responses to an EZH2-derived peptide have been identified in 7 out of 19 (37%) healthy controls. The frequency of IFNg-secreting cells ranged from 0.001–1.6% of the total CD8+ T cell pool. In the patient cohort, 4 out of 11 donors responded to the peptide (frequency 36%) with a frequency representing between 0.002 and 0.03% of CD8+ T cells. The frequency of the response is therefore comparable between the two groups. The potential role of regulatory CD4+CD25+ T cells in controlling auto-reactive immune responses to PcG proteins is being assessed. Depletion of this population can result in an increased expansion of the tumour-reactive T cell response in vitro. Thus, although ectopic expression of polycomb proteins is often seen in haemopoietic malignancy there is currently little evidence for a tumour-selective immune response in such patients.
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46

Nath, D., P. M. Slocombe, P. E. Stephens, A. Warn, G. R. Hutchinson, K. M. Yamada, A. J. Docherty, and G. Murphy. "Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells." Journal of Cell Science 112, no. 4 (February 15, 1999): 579–87. http://dx.doi.org/10.1242/jcs.112.4.579.

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Анотація:
Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to the ADAM (A Disintegrin and Metalloprotease Domain) family of proteins and is widely expressed in different tissues and cell types. Members of this family contain an amino-terminal metalloprotease domain followed by a disintegrin domain, a cysteine-rich region and a membrane proximal EGF-like domain. The disintegrin domain of metargidin contains an RGD tripeptide sequence, suggesting that it may potentially interact with the integrin family of proteins. Here we identify integrin ligands for metargidin on haemopoietic cells, by using a chimeric protein containing the extracellular domain of metargidin fused to the Fc portion of human IgG. Binding activity to a panel of human cell lines was analysed by solid-phase cell-adhesion assays. Metargidin bound to a monocytic cell line, U937, and a T cell line, MOLT-4, in a specific manner. Adhesion was divalent cation- and temperature- dependent and strongly enhanced by Mn2+, all features of integrin-mediated binding. Using a panel of anti-integrin antibodies we show that alphavbeta3 is a ligand for metargidin on U937 cells. In contrast, for MOLT-4 cells, the integrin alpha5beta1 contributes to cell binding. Adhesion was mediated by the disintegrin domain of metargidin as RGD-based peptides inhibited cell binding to both cell lines. The specificity of the interaction between both alphavbeta3 and alpha5beta1 and metargidin was further confirmed by solid-phase adhesion assays using purified recombinant integrins. These results together indicate that metargidin can function as a cell adhesion molecule via interactions with alphavbeta3 and alpha5beta1 integrins.
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47

Jia, Shu-Qin, Jian-Jun Ren, Pei-De Dong, and Xing-Kai Meng. "Probing the Hepatic Progenitor Cell in Human Hepatocellular Carcinoma." Gastroenterology Research and Practice 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/145253.

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Анотація:
Objective. The intrahepatic stem cells, also known as hepatic progenitor cells (HPCs), are able to differentiate into hepatocytes and bile duct epithelia. By exposure of different injuries and different hepatocarcinogenic regimens, the mature hepatocytes can no longer effectively regenerate; stem cells are involved in the pathogenesis of hepatocellular carcinoma.Methods. Immunohistochemistry was performed on 107 paraffin-embedded hepatocellular carcinoma specimens with the marker of hepatocyte and hepatocellular carcinoma (HepPar1), biliary differentiation (CK7,CK19), haemopoietic stem cell (HSC) (c-kit/CD117, CD34, and Thy-1/CD90), HPC specific markers (OV-6), and Ki-67, p53 protein.Results. HPCs can be identified in the tumor nodules, around the edge of tumor nodules, and in the portal tracts of the paracirrhosis nodules being positive in HepPar1, CK7, CK19, and OV-6, but they failed to immunostain with CD117, CD34, and CD90. The HPCs positive in Ki-67 are observed in the tumor and paracirrhosis tissues. In 107 specimens, 40.2% (43/107) HCC tissues expressed p53 protein, lower than that of the HPCs around the tumor nodules (46.7%, 50/107) and much higher than that of the HPCs around the paracirrhosis nodules (8.41%, 9/107).Conclusion. Human hepatocellular carcinogenesis may be based on transformation of HPCs, not HSCs, through the formation of the transitional cells (hepatocyte-like cells and bile ductal cells).
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48

Griffiths, Rebecca E., and David J. Anstee. "Normal Prion Protein Colocalises with the Tetraspanin CD63 in Cultured Human Erythroblasts." Blood 104, no. 11 (November 16, 2004): 1591. http://dx.doi.org/10.1182/blood.v104.11.1591.1591.

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Анотація:
Abstract Detailed information regarding the intracellular distribution and trafficking of prion protein (PrP) in human haemopoietic cells is lacking. In order to address this deficiency we have investigated the expression of PrP in cultured erythroid cells. CD34+ cells derived from peripheral blood were cultured in the presence of IL3, SCF and EPO and aliquots removed from the cultures at different time points for examination by confocal microscopy with monoclonal antibodies. PrP was demonstrated in the plasma membrane and, by colocalisation with organelle-specific markers, in Golgi, ER and lysosomes at all time points. PrP mRNA expression was profiled throughout the culture by QRT-PCR. PrP mRNA expression is high in the immature cells and decreases throughout the culture. PrP mRNA expression is different from erythroid specific protein expression profiles. Monoclonal antibodies to PrP and another GPI-linked protein DAF (CD55) showed distinct, non-overlapping, staining in the plasma membrane suggesting they are located in different microdomains. CD63 is a widely expressed tetraspanin thought to function in trafficking membrane proteins between the plasma membrane and intracellular organelles. All CD63 staining observed in cultured erythroid cells was colocalised with PrP. A similar concordance was not observed with CD63 and DAF. These results disclose a previously unrecognised property of PrP and suggest a general mechanism whereby PrP is recycled within cells. This mechanism may be relevant to the pathogenesis of transmissible spongiform encephalopathies.
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49

Dehal, P. K., M. J. Embleton, J. T. Kemshead, and R. E. Hawkins. "Targeted cytokine delivery to neuroblastoma." Biochemical Society Transactions 30, no. 4 (August 1, 2002): 518–20. http://dx.doi.org/10.1042/bst0300518.

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Анотація:
The aim of this study was to construct a fusion protein from the cytokine granulocyte/macrophage colony-stimulating factor (GM-CSF) and a single-chain Fv fragment (scFv D29) and to investigate its potential to activate cells of the immune system against neuroblastoma cells expressing neural cell adhesion molecule (NCAM). Mammalian cell expression of the scFv D29-GM-CSF fusion protein was compared using a number of vectors, including retroviral and adenoviral vectors. The resultant fusion protein, expressed by HeLa cells, was found by ELISA to bind immobilized recombinant NCAM. Moreover, FACS analysis confirmed binding to the human neuroblastoma cell line SKNBE and a murine neuroblastoma cell line engineered to express the glycosylphosphatidylinositol form of human NCAM (N2A-rKNIE). The fusion protein was also found to stimulate the proliferation of the FDC-P1 haemopoietic cell line, which is dependent on GM-CSF (or interleukin 3) for continued growth. In vitro clonogenic assays indicated that scFv-GM-CSF could selectively induce growth inhibition of SKNBE cells by murine lymphoid cells.
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50

De Coppi, Paolo. "Engineering tissue for the fetus: stem cells and matrix signalling." Biochemical Society Transactions 42, no. 3 (May 22, 2014): 631–35. http://dx.doi.org/10.1042/bst20140069.

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Анотація:
Congenital malformations are major causes of disease and death during the first years of life and, most of the time, functional replacement of the missing or damaged organs remains an unmet clinical need. Particularly relevant for the treatment of congenital malformation would be to collect the stem cells at diagnosis, before birth, to be able to intervene during the gestation or in the neonatal period. Human AFSCs (amniotic fluid stem cells), which have characteristics intermediate between those of embryonic and adult stem cells, have been isolated. c-Kit+Lin− cells derived from amniotic fluid display a multilineage haemopoietic potential and they can be easily reprogrammed to a pluripotent status. Although, in the future, we hope to use cells derived from the amniotic fluid, we and others have proved recently that simple organs such as the trachea can be engineered using adult progenitors utilizing decellularized cadaveric matrices. A similar approach could be used in the future for more complex organs such as the muscles, intestines or lungs.
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