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Journal articles on the topic 'Mesenchymal stromal cells derivedfrom Wharton's Jelly'

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Author: Grafiati

Published: 25 May 2024

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1

Badraiq, H., A. Cvoro, A. Galleu, M. Simon, F. Dazzi, and D. Ilic. "Maternal obesity alters characteristics of Wharton's Jelly mesenchymal stromal cells." Cytotherapy 19, no. 5 (May 2017): S160. http://dx.doi.org/10.1016/j.jcyt.2017.02.248.

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2

Lopez-Rodriguez, Y., E. Trevino, and M. L. Weiss. "Wharton's jelly mesenchymal stromal cells (WJCs) as immunoregulators in allogeneic transplantation." Placenta 32 (October 2011): S329. http://dx.doi.org/10.1016/j.placenta.2011.07.040.

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3

Majumdar, D., R. Bhonde, and I. Datta. "Influence of ischemic microenvironment on human Wharton's Jelly mesenchymal stromal cells." Placenta 34, no. 8 (August 2013): 642–49. http://dx.doi.org/10.1016/j.placenta.2013.04.021.

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4

Batsali, A., C. G. Pontikoglou, E. Kouvidi, A. Damianaki, M. Kastrinaki, and H. A. Papadaki. "Direct comparison of Wharton's Jelly and bone marrow mesenchymal stem/stromal cells." Cytotherapy 16, no. 4 (April 2014): S73—S74. http://dx.doi.org/10.1016/j.jcyt.2014.01.272.

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5

Aljitawi, Omar S., Yinghua Xiao, Da Zhang, Lisa Stehno-Bittel, Rama Garimella, Richard A. Hopkins, and Michael S. Detamore. "Generating CK19-Positive Cells with Hair-Like Structures from Wharton's Jelly Mesenchymal Stromal Cells." Stem Cells and Development 22, no. 1 (January 2013): 18–26. http://dx.doi.org/10.1089/scd.2012.0184.

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6

Panta, W., H. Kunkanjanawan, T. Kunkanjanawan, R. Parnpai, and V. Khemarangsan. "Stability characteristic of cryopreserved human umbilical cord wharton's jelly–derived mesenchymal stromal cells." Cytotherapy 21, no. 5 (May 2019): S86. http://dx.doi.org/10.1016/j.jcyt.2019.03.509.

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7

Malagon, A., M. Hautefeuille, G. Piñon, and A. Castell. "Osteogenic potential of Wharton's jelly mesenchymal stromal cells cultured on a biomimetic scaffold." Cytotherapy 22, no. 5 (May 2020): S204—S205. http://dx.doi.org/10.1016/j.jcyt.2020.04.083.

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8

Davies, John E., John T. Walker, and Armand Keating. "Concise Review: Wharton's Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells." STEM CELLS Translational Medicine 6, no. 7 (May 10, 2017): 1620–30. http://dx.doi.org/10.1002/sctm.16-0492.

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9

Zhang, Ying-Nan, Pu-Chang Lie, and Xing Wei. "Differentiation of mesenchymal stromal cells derived from umbilical cord Wharton's jelly into hepatocyte-like cells." Cytotherapy 11, no. 5 (January 2009): 548–58. http://dx.doi.org/10.1080/14653240903051533.

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10

Lupatov, A. Yu, R. Yu Saryglar, V. D. Chuprynin, S. V. Pavlovich, and K. N. Yarygin. "Comparison of the expression profile of surface molecular markers on mesenchymal stromal cell cultures isolated from human endometrium and umbilical cord." Biomeditsinskaya Khimiya 63, no. 1 (January 2017): 85–90. http://dx.doi.org/10.18097/pbmc20176301085.

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Endometrial mesenchymal stromal cells (eMSCs), along with mesenchymal stromal cells (MSCs) isolated from other tissues, are promising for use in regenerative medicine. The benefits of eMSCs include their presence in adults, simplicity of isolation, high proliferative and differentiation capacity. In this study, we have employed the flow cytometry technique to assess expression of 28 molecular markers on the surface of two eMSCs cultures. The culture of MSCs isolated from Wharton's jelly of the umbilical cord (uMSCs) was used as a reference, because uMSCs were studied in details earlier and demonstrated their effectiveness in vivo. Both types of MSCs demonstrated similar expression profiles. They included stem cells surface molecules, cell adhesion molecules and their ligands, some receptor molecules responsible for cell metabolism and proliferation, as well as immunological response molecules.

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11

Datta, Indrani, Swati Mishra, Lipsa Mohanty, Sunitha Pulikkot, and Preeti G. Joshi. "Neuronal plasticity of human Wharton's jelly mesenchymal stromal cells to the dopaminergic cell type compared with human bone marrow mesenchymal stromal cells." Cytotherapy 13, no. 8 (September 2011): 918–32. http://dx.doi.org/10.3109/14653249.2011.579957.

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12

Shohara, Ryutaro, Akihito Yamamoto, Sachiko Takikawa, Akira Iwase, Hideharu Hibi, Fumitaka Kikkawa, and Minoru Ueda. "Mesenchymal stromal cells of human umbilical cord Wharton's jelly accelerate wound healing by paracrine mechanisms." Cytotherapy 14, no. 10 (September 2012): 1171–81. http://dx.doi.org/10.3109/14653249.2012.706705.

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13

Govindasamy, V., M. Chai, Z. Lee, K. Then, S. Cheong, and N. Abu Kasim. "Wharton's jelly mesenchymal stromal cells express pancreatic lineage markers upon culturing in hanging drop technique." Cytotherapy 20, no. 5 (May 2018): S39. http://dx.doi.org/10.1016/j.jcyt.2018.02.096.

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14

Manochantr, S., Y. U-pratya, P. Kheolamai, S. Rojphisan, M. Chayosumrit, C. Tantrawatpan, A. Supokawej, and S. Issaragrisil. "Immunosuppressive properties of mesenchymal stromal cells derived from amnion, placenta, Wharton's jelly and umbilical cord." Internal Medicine Journal 43, no. 4 (April 2013): 430–39. http://dx.doi.org/10.1111/imj.12044.

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15

Vivas Pradillo, D., L. Martorell, R. Cabrera-Pérez, C. Mirabel, C. Frago, J. Ayats, M. Monguió-Tortajada, et al. "Toward the use of Wharton's Jelly-derived multipotent Mesenchymal Stromal Cells in bone Tissue Engineering strategies." Cytotherapy 20, no. 5 (May 2018): S55. http://dx.doi.org/10.1016/j.jcyt.2018.02.152.

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16

SV, Konovalov, Moroz VM, Husakova IV, Deryabina OG, and Tochilovskyi AA. "Comparative influence of mesenchymal stromal cells of different origin on DNA fragmentation of neuronal nuclei during ischemia-reperfusion of the somatosensory cortex of the rat brain." Advances in Tissue Engineering & Regenerative Medicine: Open Access 9, no. 1 (September 18, 2023): 29–33. http://dx.doi.org/10.15406/atroa.2023.09.00138.

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Relevance: One of the main causes of stroke in acute cerebrovascular accident (ACVA) is ischemia, which begins with the formation of an acute neuronal energy deficit with subsequent activation of the "ischemic cascade" reactions that lead to irreversible damage to nervous tissue. Aim: To compare the effect of mesenchymal stromal cells (MSCs) of different origin and human MSCs from Wharton's jelly lysate on neuroapoptotic changes in the somatosensory cortex of the rat brain in conditions of model ischemia-reperfusion (IR) performed by ductal cytoflowmetry. Materials and methods: The experiment was carried out using 165 four-month-old male Wistar rats weighing 160-190 g, which were subjected to bilateral 20-minute transient ischemia-reperfusion (IR) of the internal carotid arteries. After modeling the pathology, the animals were injected into the femoral vein (iv) with MSCs obtained from umbilical cord Wharton jelly, human and rat adipose tissue in the amount of 106 cells/animal. Other groups of experimental animals were intravenously injected with fetal rat fibroblasts in the amount of 106 cells/animal (in 0.2 ml of physiological solution) and MSCs from umbilical cord Wharton's jelly lysate in a dose of 0.2 ml/animal. Control animals were injected intravenously with 0.2 ml of physiological solution. The level of DNA fragmentation in the nuclei of neurons of the somatosensory cortex of rats on the 7th day after ischemia-reperfusion was studied by flow cytometry. The research was carried out on a flow cytometer "Partech РАС" of the company Partech, Germany. The statistical significance of the differences was assessed by Student's t-test. Results: The study noted an increase in the level of fragmented DNA in a group of animals with IR by 3.25 times 7 days after model IR. The performed treatment showed that in groups with transplanted MSCs of various origins and MSC lysate from human Wharton's jelly cells, the intensity of DNA fragmentation in the nuclei of neurons in rat brain somatosensory cortex reliably decreased in1.8-2. 6 times compared with the group of control pathology (IR without treatment). Conclusions: Experimental 20-minute IR of the brain of rats forms a persistent focus of necrotic and apoptotic death of neurons, which is manifested by an increase in fragmented DNA (3.25 times). Intravenous transplantation of MSCs of various origin and lysate of MSCs from human Wharton jelly has a therapeutic effect in model IR, which is manifested by a decrease in the processes of neuro-destruction and neuroapoptosis in the area of ischemic brain damage Such effect is a link to the polytrophic mechanism of MSCs neuro-protective action.

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17

Wu, Li-Fang, Ni-Na Wang, Yuan-Sheng Liu, and Xing Wei. "Differentiation of Wharton's Jelly Primitive Stromal Cells into Insulin-Producing Cells in Comparison with Bone Marrow Mesenchymal Stem Cells." Tissue Engineering Part A 15, no. 10 (October 2009): 2865–73. http://dx.doi.org/10.1089/ten.tea.2008.0579.

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18

Aljitawi, Omar S., Peggy Keefe, Lindsey Ott, Dandan Li, Da Zhang, Sunil Abhyankar, Rama Garimella, Joseph McGuirk, and Michael Detamore. "A Wharton's Jelly Mesenchymal Stromal Cell Derived 3D Osteogenic Niche Allows for Cord Blood Stem Cell Attachment." Blood 118, no. 21 (November 18, 2011): 4813. http://dx.doi.org/10.1182/blood.v118.21.4813.4813.

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Abstract Abstract 4813 Background: Most of umbilical cord blood (UCB) stem cell ex vivo expansion methods have led to UCB stem cell differentiation instead of their self-renewal. Evidence suggests that bone osteoblastic cells are responsible, through physical contact with hematopoietic stem cells (HSCs), for the maintenance of long-term HSCs. Aims: To develop a 3 dimensional (3D) osteogenic structure that provides a niche for UCB stem cells and secondarily, assess the ability of this structure, in addition, to a cocktail of cytokines to expand UCB stem cells.> Methods: Mesenchymal stromal cells (MSCs) isolated form Wharton's Jelly (WJ) were seeded into biodegradable scaffolds followed by osteogenic differentiation induction using osteogenic differentiation media for up to 4 and 6 weeks to develop a 4-week and a 6-week osteogenic scaffolds, respectively. CD34+ selected UCB stem cells were expanded on a monolayer of WJMSCs using a cocktail of cytokines for one week, following which the monolayer and expanded CD34+ UCB stem cells were trypsinized and added to the 4-week and 6-week 3D osteogenic scaffolds (3D conditions), or plated again in culture flask (2D conditions). Pre- and post-expansion total nucleated cell counts were determined and flow cytometry was used to assess the phenotype of the expanded population. Results: Osteogenic differentiation was successfully induced in 3D scaffolds as evident by Alizarin-red staining, scanning electron microscopy (SEM) and molecular testing. UCB stem cell attachment to the osteogenic scaffold was verified by SEM. TNCs were expanded 10X in 2D and 200X in 3D conditions. However, the percentage of CD34+ cells was 5.31% and 4.91% in 2D, and 2.98% and 1.14% in 4-week and 6-week 3D conditions, respectively. Conclusion: Attachment of CD34+ UCB stem cells to 3D osteogenic scaffold allowed for their expansion, though the majority of the expanded cells lost their CD34 expression possibly secondary to their differentiation. Disclosures: No relevant conflicts of interest to declare.

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19

Balasubramanian, Sudha, Parvathy Venugopal, Swathi Sundarraj, Zubaidah Zakaria, Anish Sen Majumdar, and Malancha Ta. "Comparison of chemokine and receptor gene expression between Wharton's jelly and bone marrow-derived mesenchymal stromal cells." Cytotherapy 14, no. 1 (January 2012): 26–33. http://dx.doi.org/10.3109/14653249.2011.605119.

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20

Hou, Tianyong, Jianzhong Xu, Xuehui Wu, Zhao Xie, Fei Luo, Zehua Zhang, and Ling Zeng. "Umbilical Cord Wharton's Jelly: A New Potential Cell Source of Mesenchymal Stromal Cells for Bone Tissue Engineering." Tissue Engineering Part A 15, no. 9 (September 2009): 2325–34. http://dx.doi.org/10.1089/ten.tea.2008.0402.

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21

Panta, W., T. Yoisungnern, S. Imsoonthornruksa, S. Suksaweang, M. Ketudat-Cairns, and R. Parnpai. "Enhance hepatic differentiation of human Wharton's jelly–derived mesenchymal stromal cells by using sodium butyrate pre-treated." Cytotherapy 21, no. 5 (May 2019): S83. http://dx.doi.org/10.1016/j.jcyt.2019.03.499.

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22

Lopez, Yelica. "Evaluating the Impact of Oxygen Concentration and Plating Density on Human Wharton's Jelly-Derived Mesenchymal Stromal Cells." Open Tissue Engineering and Regenerative Medicine Journal 4, no. 1 (December 30, 2011): 82–94. http://dx.doi.org/10.2174/1875043501104010082.

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23

Cason, Carolina, Giuseppina Campisciano, Nunzia Zanotta, Erica Valencic, Serena Delbue, Ramona Bella, and Manola Comar. "SV40 Infection of Mesenchymal Stromal Cells From Wharton's Jelly Drives the Production of Inflammatory and Tumoral Mediators." Journal of Cellular Physiology 232, no. 11 (December 29, 2016): 3060–66. http://dx.doi.org/10.1002/jcp.25723.

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24

Choi, Moran, Hyun-Sun Lee, Purevjargal Naidansaren, Hyun-Kyung Kim, Eunju O, Jung-Ho Cha, Hyun-Young Ahn, Park In Yang, Jong-Chul Shin, and Young Ae Joe. "Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels." International Journal of Biochemistry & Cell Biology 45, no. 3 (March 2013): 560–70. http://dx.doi.org/10.1016/j.biocel.2012.12.001.

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25

Gladysz, D., A. Krzywdzinska, M. Murzyn, K. Kapturska, K. K. Hozyasz, and T. Oldak. "The influence of Wharton's jelly-derived mesenchymal stromal cells on T regulatory cells in patients with autism spectrum disorder." Cytotherapy 20, no. 5 (May 2018): S97—S98. http://dx.doi.org/10.1016/j.jcyt.2018.02.287.

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26

Frausin, Stefano, Serena Viventi, Lucia Verga Falzacappa, Miriana Jlenia Quattromani, Giampiero Leanza, Alberto Tommasini, and Erica Valencic. "Wharton's jelly derived mesenchymal stromal cells: Biological properties, induction of neuronal phenotype and current applications in neurodegeneration research." Acta Histochemica 117, no. 4-5 (May 2015): 329–38. http://dx.doi.org/10.1016/j.acthis.2015.02.005.

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27

Najar, Mehdi, Gordana Raicevic, Hicham Id Boufker, Hussein Fayyad-Kazan, Cécile De Bruyn, Nathalie Meuleman, Dominique Bron, Michel Toungouz, and Laurence Lagneaux. "Adipose-Tissue-Derived and Wharton's Jelly–Derived Mesenchymal Stromal Cells Suppress Lymphocyte Responses by Secreting Leukemia Inhibitory Factor." Tissue Engineering Part A 16, no. 11 (November 2010): 3537–46. http://dx.doi.org/10.1089/ten.tea.2010.0159.

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28

Oliver-Vila, Irene, Maria Isabel Coca, Marta Grau-Vorster, Noèlia Pujals-Fonts, Marta Caminal, Alba Casamayor-Genescà, Isabel Ortega, et al. "Evaluation of a cell-banking strategy for the production of clinical grade mesenchymal stromal cells from Wharton's jelly." Cytotherapy 18, no. 1 (January 2016): 25–35. http://dx.doi.org/10.1016/j.jcyt.2015.10.001.

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29

Boey, K. P., D. S. Lim, C. Ong, J. Mesilamani, K. Tang, M. Li, P. Zhu, and T. T. Phan. "Comparison of extraction methods and culture medium for umbilical cord lining- and wharton's jelly-derived mesenchymal stromal cells." Cytotherapy 21, no. 5 (May 2019): S80. http://dx.doi.org/10.1016/j.jcyt.2019.03.489.

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30

Hang, Zhao, and Xiao Haijun. "Proliferative, Differentiative, and Immunological Characteristics of Chondro-Differentiated Mesenchymal Stromal Cells Derived from Rabbit Umbilical Cord Wharton's Jelly." Journal of Biomaterials and Tissue Engineering 8, no. 7 (July 1, 2018): 1046–52. http://dx.doi.org/10.1166/jbt.2018.1833.

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31

Lee, Hyun-Sun, Kwang S. Kim, Hee-Suk Lim, Moran Choi, Hyun-Kyung Kim, Hyun-Young Ahn, Jong-Chul Shin, and Young Ae Joe. "Priming Wharton's Jelly-Derived Mesenchymal Stromal/Stem Cells With ROCK Inhibitor Improves Recovery in an Intracerebral Hemorrhage Model." Journal of Cellular Biochemistry 116, no. 2 (December 12, 2014): 310–19. http://dx.doi.org/10.1002/jcb.24969.

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32

Sharma, Tulika, Poonam Kumari, Neha Pincha, Naresh Mutukula, Shekhar Saha, Siddhartha S. Jana, and Malancha Ta. "Inhibition of non-muscle myosin II leads to G0/G1 arrest of Wharton's jelly-derived mesenchymal stromal cells." Cytotherapy 16, no. 5 (May 2014): 640–52. http://dx.doi.org/10.1016/j.jcyt.2013.09.003.

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33

Oppliger, Byron, Marianne S. Joerger-Messerli, Cedric Simillion, Martin Mueller, Daniel V. Surbek, and Andreina Schoeberlein. "Mesenchymal stromal cells from umbilical cord Wharton's jelly trigger oligodendroglial differentiation in neural progenitor cells through cell-to-cell contact." Cytotherapy 19, no. 7 (July 2017): 829–38. http://dx.doi.org/10.1016/j.jcyt.2017.03.075.

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34

Milazzo, Luisa, Francesca Vulcano, Alessandra Barca, Giampiero Macioce, Emanuela Paldino, Stefania Rossi, Carmela Ciccarelli, Hamisa J. Hassan, and Adele Giampaolo. "Cord blood CD34+ cells expanded on Wharton's jelly multipotent mesenchymal stromal cells improve the hematopoietic engraftment in NOD/SCID mice." European Journal of Haematology 93, no. 5 (May 26, 2014): 384–91. http://dx.doi.org/10.1111/ejh.12363.

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35

Batsali, Aristea, Charalampos Pontikoglou, Elisavet Kouvidi, Athina Damianaki, Aikaterini Stratigi, Maria-Christina Kastrinaki, and Helen A. Papadaki. "Comparative Analysis Of Bone Marrow and Wharton’s Jelly Mesenchymal Stem/Stromal Cells." Blood 122, no. 21 (November 15, 2013): 1212. http://dx.doi.org/10.1182/blood.v122.21.1212.1212.

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Abstract Bone narrow (BM)- derived mesenchymal stem/stromal cells (MSCs) represent the most extensively studied population of adult MSCs and are considered as the gold-standard for MSC-based clinical applications. Yet, it is now becoming increasingly clear that BM may not represent the most suitable source for MSC collection. Indeed, Umbilical cord (UC) has emerged as a more abundant and easily attainable source of MSCs and several reports have shown that MSCs can be efficiently isolated from the connective tissue that surrounds UC vessels, namely the Wharton's jelly (WJ). According to the existing literature, WJ-MSCs display typical MSC characteristics, however a head-to-head comparison with BM-MSCs is still lacking. Provided that ex vivo MSC expansion is a prerequisite for clinical MSC-applications, in the present study we seek to comparatively investigate the characteristics of WJ- and BM-MSCs, cultured under identical conditions. MSCs were isolated and expanded from consenting healthy donors’ BM aspirates (n=5) and from the WJ of full-term neonates (n=10) after written informed consent of the family. MSCs were in vitro expanded and re-seeded for a total of 10 passages (P) and phenotypically characterized by flow cytometry (FC). MSCs were induced to differentiate in vitro to adipocytes and osteoblasts. Differentiation was assessed by cytochemical stains and by the expression of adipocyte- and osteocyte-specific genes. Relative gene expression was calculated by the ΔCt method. MSC growth characteristics were assessed by evaluating the population doubling time (DT) and by a methyl-triazolyl-tetrazolium (MTT)-assay throughout passages. Cell-cycle analysis was performed using propidium iodide (PI) staining. MSC survival was evaluated by FC with 7-Aminoactinomycin D (7-AAD) and senescence was estimated by the percentage of SA-b-gal+ cells in cultures. Moreover, MSC karyotypic stability was assessed with classic G-banding. Finally the expression of genes related to Wnt-mediated signal transduction was also investigated, using a PCR array. Total RNA was thus isolated from 6 representative BM- and 6 WJ-MSC cultures at P2. The fold change (FC) for each gene between the group of WJ- and the group of BM-MSCs was calculated with the ΔΔCt method (FC=2-ΔΔCt). WJ-MSCs displayed a spindle-shape morphology, similar to BM-MSCs. Furthermore, WJ- and BM-MSCs displayed identical immunophenotype, as evidenced by the expression of CD90,CD105,CD44,CD29,CD73 and the lack of expression of CD45,CD14,CD34,CD31. WJ-MSCs displayed superior proliferative potential compared to BM-MSCs throughout passages (p<0.05). Moreover, the proportion of proliferating (S/G2/M) WJ-MSCs was higher compared to BM-MSCs at P4 (p<0.001), while there was no significant difference between two MSC populations in the proportion of 7-AADbright/dim –cells at P4. Regarding senescence, significantly fewer SA-b-gal+ cells were observed in WJ-MSC cultures, as compared to BM-MSCs at P10 (p<0.05). Compared to their bone marrow counterparts, WJ-MSCs displayed inferior capacity to differentiate into adipocytes and osteoblasts as evidenced by Oil Red O and Alizarin Red staining, respectively, and also by the weaker expression of adipocyte- (PPAR-g, p<0.0002; CEBP-a, p<0.0001) and osteocyte-specific markers (RUNX2, p<0.0006; DLX5, p<0.0001; ALP, p<0.0042). No chromosomal abnormalities were observed in either WJ- or BM-MSCs during in vitro expansion. Regarding the Wnt-pathway signaling molecules, the Wnt antagonist sFRP4, which induces adipogenesis, as well the Wnt/b-catenin target gene Wisp-1, a regulator of osteogenesis were significantly down-regulated in WJ-MSCs (FC=22.3825, p<0,05; FC=20.18, p<0.0001, respectively). On the other hand, the expression of Wnt/b-catenin target gene Cyclin D1, which induces MSC proliferation and represses adipogenesis, was up-regulated in WJ-MSCs (FC=2.8, p<0.05). Taken together WJ-MSCs display decreased cellular senescence after extended in vitro culture, increased proliferative capacity and reduced potential to differentiate in vitro to adipocytes and osteocytes, as compared to BM-MSCs. The last two observations can be explained, at least partly, by the aberrant expression of Wnt-signaling molecules in WJ-MSCs. The emerging role of Wnt-signaling pathway in WJ-MSC biology is currently under investigation. Disclosures: No relevant conflicts of interest to declare.

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36

Batsali, Aristea, Charalampos Pontikoglou, Emmanuel Agrafiotis, Elisavet Kouvidi, Irene Mavroudi, Athina Damianaki, Maria-Christina Kastrinaki, and Helen Papadaki. "Emerging Roles of Wisp-1 and SFRP4 in Proliferation and Differentiation Potential of Wharton's Jelly Mesenchymal Stem/Stromal Cells." Blood 124, no. 21 (December 6, 2014): 4375. http://dx.doi.org/10.1182/blood.v124.21.4375.4375.

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Abstract We have previously shown (Batsali A et al., Blood 2013:122, 1212) that ex vivo expanded human mesenchymal stem/stromal cells (MSCs) derived from the Wharton's jelly (WJ) of the umbilical cord exhibit increased proliferative capacity and reduced potential to differentiate in vitro to adipocytes and osteocytes, compared to bone marrow (BM) derived-MSCs. Provided that the WNT-pathways are involved in proliferation and differentiation of BM-MSCs, we assumed that the aforementioned findings might be attributed, at least in part, to aberrant WNT-signaling in WJ-MSCs. In support of this hypothesis, we found that gene expression of the Wnt antagonist sFRP4, a promoter of adipogenesis in human adipose tissue-derived MSCs, was significantly down-regulated in WJ-MSCs and that mRNA levels of WNT-induced secreted protein-1, (WISP-1), a regulator of osteogenesis in BM-MSCs, were also significantly reduced in WJ-MSCs. These observations imply a connection between these WNT-associated molecules and the biological properties of WJ-MSCs, which requires, however, further investigation. The present study was undertaken so as to explore the effects of WISP-1 and sFRP4 in growth and differentiation of ex-vivo expanded WJ-MSCs. MSCs were isolated from consenting healthy donors’ BM aspirates (n=5) and from the WJ of full-term neonates (n=5) after written informed consent of the family. MSCs were in vitro expanded, re-seeded for a total of 4 passages (P) and phenotypically characterized by flow cytometry at P3. WJ-MSCs were grown in the absence or presence of rhWISP-1 or rhsFRP4 and cell proliferation was assessed by a methyl-triazolyl-tetrazolium (MTT)-assay. In addition, WJ-MSCs were induced to differentiate in vitro to osteoblasts and adipocytes, in the absence or presence of rhWISP-1 or rhsFRP4 respectively. Differentiation was quantified by cytochemical stains and by the expression of adipocyte- and osteocyte-specific genes by real time RT-PCR. Relative gene expression was calculated by the ΔCt method. The expression of WISP-1 and sFRP4 by non-differentiated WJ- and BM-MSCs as well as by WJ-MSCs during osteogenesis and adipogenesis, respectively, was also evaluated by real time RT-PCR. Culture-expanded cells from both WJ and BM displayed typical morphological and immunophenotypic MSC characteristics and were able to differentiate into osteoblasts and adipocytes. In line with our previous work WISP-1 and sFRP4 mRNA were significantly decreased in WJ-MSCs, compared to BM-MSCs. To explore the role of WISP-1 in WJ-MSCs' growth we cultured cells in the presence of 50 ng/ml or 100 ng/ml rhWISP1 and assessed cell proliferation at multiple time points, throughout a 14-day culture. WISP-1 treatment did not lead to any significant effect in cell numbers. Next, we investigated the time course of WISP1 gene expression during osteoinduction. In all samples, WISP1 mRNA levels increased during osteogenesis. As compared to day0 (exposure to osteogenic medium), the increase in gene expression reached statistical significance at days 7 and 14. Furthermore, WISP-1 gene expression was significantly higher at day 14, compared to day 7. To investigate the functional effects of WISP1 on the osteoblastic differentiation of WJ-MSCs, cells were cultured for 7 days in osteogenic medium supplemented with 50ng/ml rh-WISP1. A significant increase in the expression of RUNX2 and ALP was detected, compared to non-treated cells. To investigate the impact of sFRP4 in WJ-MSC's proliferation we exposed cells to 20nM rhsFRP4 for 14 days. Live cell numbers, at various time points, were significantly reduced in treated cells. Regarding the time course of sFRP4 expression during adipogenic differentiation, sFRP4 mRNA levels increased during adipogenesis reaching statistical significance at days7 and 14, as compared to day0. In addition, sFRP4 gene expression was significantly higher at day 14 as compared to day 7. Finally, when cells underwent adipogenic differentiation in the presence of rhSFRP4, a significant increase in PPARG and CEBPA mRNA levels was detected at day 14, as compared to non-treated cells Collectively, our results suggest that WISP-1 and sFRP4 may be actively implicated in proliferation and differentiation of WJ-MSCs. The functional role of these WNT-related molecules in the biology of WJ-MSCs requires deeper understanding, in view of the growing interest for the use of WJ-MSCs in cell-based therapies. Disclosures No relevant conflicts of interest to declare.

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De Bruyn, Cécile, Mehdi Najar, Gordana Raicevic, Nathalie Meuleman, Karlien Pieters, Basile Stamatopoulos, Alain Delforge, Dominique Bron, and Laurence Lagneaux. "A Rapid, Simple, and Reproducible Method for the Isolation of Mesenchymal Stromal Cells from Wharton's Jelly Without Enzymatic Treatment." Stem Cells and Development 20, no. 3 (March 2011): 547–57. http://dx.doi.org/10.1089/scd.2010.0260.

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Quaranta, Paola, Daniele Focosi, Marilena Di Iesu, Chiara Cursi, Alessandra Zucca, Michele Curcio, Simone Lapi, et al. "Human Wharton's jelly–derived mesenchymal stromal cells engineered to secrete Epstein-Barr virus interleukin-10 show enhanced immunosuppressive properties." Cytotherapy 18, no. 2 (February 2016): 205–18. http://dx.doi.org/10.1016/j.jcyt.2015.11.011.

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Coll, R., J. Vidal, H. Kumru, J. Benito, M. Valles, N. Ribó, M. Codinach, et al. "Intrathecal administration of expanded wharton's jelly mesenchymal stromal cells (WJ-MSC) in chronic traumatic spinal cord injury (SCI) (NCT03003364)." Cytotherapy 20, no. 5 (May 2018): S33—S34. http://dx.doi.org/10.1016/j.jcyt.2018.02.082.

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Coll, R., J. Vidal, H. Kumru, J. Benito, M. Valles, M. Codinach, M. Blanco, et al. "Is HLA matching relevant for treating Spinal Cord Injury with intrathecal administration of expanded Wharton's Jelly Mesenchymal Stromal Cells?" Cytotherapy 22, no. 5 (May 2020): S26—S27. http://dx.doi.org/10.1016/j.jcyt.2020.03.006.

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Fernández, A. López, I. Carreras Sánchez, and J. Vives. "Successful scale up expansion of Wharton's jelly mesenchymal stromal cells in different commercial xeno-free and serum-free media." Cytotherapy 22, no. 5 (May 2020): S94. http://dx.doi.org/10.1016/j.jcyt.2020.03.162.

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Pochon, Cecile, Romain Perouf, Allan Bertrand, Anne-Béatrice Notarantonio, Naceur Charif, Marcelo De Carvalho Bittencourt, Guillemette Fouquet, et al. "IFN-γ Primed Wharton's Jelly Mesenchymal Stromal Cells Inhibit T Cell Proliferation By Synergistic IDO and Mitochondrial Transfer Mechanisms." Blood 140, Supplement 1 (November 15, 2022): 4504–5. http://dx.doi.org/10.1182/blood-2022-167814.

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Kaushik, Komal, and Amitava Das. "Cycloxygenase-2 inhibition potentiates trans-differentiation of Wharton's jelly–mesenchymal stromal cells into endothelial cells: Transplantation enhances neovascularization-mediated wound repair." Cytotherapy 21, no. 2 (February 2019): 260–73. http://dx.doi.org/10.1016/j.jcyt.2019.01.004.

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Wang, Ying, Feng Chen, Bing Gu, Guanghua Chen, Huirong Chang, and Depei Wu. "Mesenchymal Stromal Cells as an Adjuvant Treatment for Severe Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation." Acta Haematologica 133, no. 1 (August 16, 2014): 72–77. http://dx.doi.org/10.1159/000362530.

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The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic hematopoietic stem cell transplantation (HSCT) is still challenging. Because mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair-promoting properties, we retrospectively analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During treatment, each patient received at least one MSC infusion of Wharton's jelly derived from the umbilical cord of a third-party donor. In 6 patients, MSC treatment was initiated within 3 days of gross hematuria onset, while the 7th patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) × 106/kg. Five of 7 patients responded to treatment. Notably, gross hematuria promptly disappeared in 3 patients after 1 infusion, with a time to remission not seen in patients without MSC infusion. Two patients showed no response even after several infusions. No acute or late complications were recorded. Our findings indicate that MSC transfusion might be a feasible and safe supplemental therapy for patients with severe LO-HC after allogeneic HSCT.

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Jing, Bai, Hu Yuan, Wang Yi-Ru, Liu Li-Feng, Chen Jie, Su Shao-Ping, and Wang Yu. "Comparison of human amniotic fluid-derived and umbilical cord Wharton's Jelly-derived mesenchymal stromal cells: Characterization and myocardial differentiation capacity." Journal of Geriatric Cardiology 9, no. 2 (July 20, 2012): 166–71. http://dx.doi.org/10.3724/sp.j.1263.2011.12091.

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Bai, Jing, and Yu Wang. "COMPARISON OF HUMAN AMNIOTIC FLUID-DERIVED AND UMBILICAL CORD WHARTON'S JELLY-DERIVED MESENCHYMAL STROMAL CELLS: CHARACTERISATION AND MYOCARDIAL DIFFERENTIATION CAPACITY." Heart 98, Suppl 2 (October 2012): E67.3—E68. http://dx.doi.org/10.1136/heartjnl-2012-302920a.167.

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van der Garde, Mark, Melissa van Pel, Jose Eduardo Millán Rivero, Alice de Graaf-Dijkstra, Manon C. Slot, Yoshiko Kleinveld, Suzanne M. Watt, Helene Roelofs, and Jaap Jan Zwaginga. "Direct Comparison of Wharton's Jelly and Bone Marrow-Derived Mesenchymal Stromal Cells to Enhance Engraftment of Cord Blood CD34+Transplants." Stem Cells and Development 24, no. 22 (November 15, 2015): 2649–59. http://dx.doi.org/10.1089/scd.2015.0138.

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Moreira, Alvaro, Caitlyn Winter, Jooby Joy, Lauryn Winter, Maxwell Jones, Michelle Noronha, Melissa Porter, et al. "Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia." STEM CELLS Translational Medicine 9, no. 2 (November 27, 2019): 221–34. http://dx.doi.org/10.1002/sctm.18-0273.

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Vulcano, Francesca, Luisa Milazzo, Carmela Ciccarelli, Adriana Eramo, Giovanni Sette, Annunziata Mauro, Giampiero Macioce, et al. "Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer." Experimental Cell Research 345, no. 2 (July 2016): 190–98. http://dx.doi.org/10.1016/j.yexcr.2016.06.003.

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van der Garde, Mark, Melissa Van Pel, Jose Millan Rivero, Alice de Graaf-Dijkstra, Manon Slot, Yoshiko Kleinveld, Suzanne Watt, Helene Roelofs, and Jaap Jan Zwaginga. "Direct Comparison of Wharton Jelly and Bone Marrow Derived Mesenchymal Stromal Cells to Enhance Engraftment of Cord Blood CD34+ Transplants." Blood 126, no. 23 (December 3, 2015): 5410. http://dx.doi.org/10.1182/blood.v126.23.5410.5410.

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Abstract Co-transplantation of CD34+ hematopoietic stem and progenitor cells (HSPC) and mesenchymal stromal cells (MSC) enhances HSPC engraftment. For these applications, MSC are mostly obtained from bone marrow. However, MSC can also be sourced from Wharton's jelly (WJ) of the human umbilical cord, which as a 'waste product', is cheaper to acquire and without significant burden to the donor. Here, we evaluated the ability of WJ MSC to enhance HSPC engraftment. First, we compared cultured human WJ MSC with human bone marrow-derived MSC (BM MSC) for in vitro marker expression, immunomodulatory capacity and differentiation into three mesenchymal lineages. Although we confirmed that WJ MSC have a more restricted differentiation capacity, both WJ MSC and BM MSC expressed similar levels of surface markers and exhibited similar immune inhibitory capacities. Co-transplantation of either WJ MSC or BM MSC with CB CD34+ cells into NOD-SCID mice showed faster recovery of human platelets and CD45+ cells in the peripheral blood and a 3-fold higher engraftment in the BM, blood and spleen six weeks after transplantation when compared to transplantation of CD34+ cells alone. Upon co-incubation, both MSC sources increased the expression of adhesion molecules on CD34+ cells, although SDF-1-induced migration of CD34+ cells remained unaltered. Interestingly, there was an increase in CFU-GEMM when CB CD34+ cells were cultured on monolayers of WJ MSC in the presence of exogenous thrombopoietin, and an increase in BFU-E when BM MSC replaced WJ MSC in such cultures. Our results suggest that WJ MSC is likely to be a practical alternative for BM MSC to enhance CB CD34+ cell engraftment. Disclosures No relevant conflicts of interest to declare.

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