Abstract
Mesenchymal stem cells (MSCs) from bone marrow, adult organs and fetuses face the disadvantages of invasive isolation, limited cell numbers and ethical constraints while embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) face the clinical hurdles of potential immunorejection and tumorigenesis respectively. These challenges have prompted interest in the study and evaluation of stem cells from birth-associated tissues. The umbilical cord (UC) has been the most popular. Hematopoietic stem cells (HSCs) harvested from cord blood have been successfully used for the treatment of hematopoietic diseases. Stem cell populations have also been reported in other compartments of the UC viz., amnion, subamnion, perivascular region, Wharton’s jelly, umbilical blood vessel adventia and endothelium. Differences in stemness characteristics between compartments have been reported and hence derivation protocols using whole UC pieces containing all compartments yield mixed stem cell populations with varied characteristics. Stem cells derived directly from the uncontaminated Wharton’s jelly (hWJSCs) appear to offer the best clinical utility because of their unique beneficial properties. They are non-controversial, can be harvested painlessly in abundance, proliferative, possess stemness properties that last several passages in vitro, multipotent, hypoimmunogenic and do not induce tumorigenesis even though they have some ESC markers. hWJSCs and its extracts (conditioned medium and lysate) also possess anti-cancer properties and support HSC expansion ex vivo. They are thus attractive autologous or allogeneic agents for the treatment of malignant and non-malignant hematopoietic and non-hematopoietic diseases. This review critically evaluates their therapeutic value, the challenges and future directions for their clinical application.
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Laurent, L. C., Ulitsky, I., Slavin, I., et al. (2011). Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell, 8, 106–118.
Ben-David, U., & Benvenisty, N. (2011). The tumorigenicity of human embryonic and induced pluripotent stem cells. Nature Reviews Cancer, 11, 268–277.
Gutierrez-Aranda, I., Ramos-Mejia, V., Bueno, C., et al. (2010). Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells, 28, 1568–1570.
Bongso, A., Fong, C. Y., & Gauthaman, K. (2008). Taking stem cells to the clinic: major challenges. Journal of Cellular Biochemistry, 105, 1352–1360.
Pappa, K. I., & Anagnou, N. P. (2009). Novel sources of fetal stem cells: where do they fit on the developmental continuum? Future Medicine, 4, 423–433.
Weiss, M. L., & Troyer, D. L. (2006). Stem cells in the umbilical cord. Stem Cell Reviews, 2, 155–162.
De-Miguel, M. P., Arnalich-Montiel, F., Lopez-Iglesias, P., Blazquez-Martinez, A., & Nistal, M. (2009). Epiblast-derived stem cells in embryonic and adult tissues. International Journal of Developmental Biology, 53, 1529–1540.
Henderson, J. K., Draper, J. S., Baillie, H. S., et al. (2002). Preimplantation human embryos and embryonic stem cells show comparable expression of stage-specific embryonic antigens. Stem Cells, 20, 329–337.
William, P. L., Banister, L. H., Berry, M. M., et al. (1995). Grays anatomy (38th ed.). London: ELBS Churchill Livingstone.
Jeschke, M. G., Gauglitz, G. G., Phan, T. T., Herndon, D. N., & Kita, K. (2011). Umbilical cord lining membrane and Wharton’s jelly-derived mesenchymal stem cells: the similarities and differences. Open Tissue Engineering and Regenerative Medicine Journal, 4, 21–27.
Conconi, M. T., Di Liddo, R., Tommasini, M., Calore, C., & Parnigotto, P. P. (2011). Phenotype and differentiation potential of stromal populations obtained from various zones of human umbilical cord: an overview. Open Tissue Engineering and Regenerative Medicine Journal, 4, 6–20.
Weiss, M. L., Medicetty, S., Bledsoe, A. R., Rachakatla, R. S., Choi, M., & Merchav, S. (2006). Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells, 24, 781–792.
Seshareddy, K., Troyer, D., & Weiss, M. L. (2008). Methods to isolate mesenchymal-like cells from Wharton’s jelly of umbilical cord. Methods in Cell Biology, 86, 101–119.
Wang, H. S., Hung, S. C., Peng, S. T., et al. (2004). Mesenchymal stem cells in the Wharton’s Jelly of the human umbilical cord. Stem Cells, 22, 1330–1337.
Fong, C. Y., Richards, M., Manasi, N., Biswas, A., & Bongso, A. (2007). Comparative growth behaviour and characterization of stem cells from human Wharton’s jelly. Reproductive Biomedicine Online, 15, 708–718.
Fong, C. Y., Gauthaman, K., & Bongso, A. (2009). Reproductive stem cells of embryonic origin: comparative properties and potential benefits of human embryonic stem cells and Wharton’s jelly stem cells. In C. Simon & A. Pellicer (Eds.), AStem cells in human reproduction (2nd ed., pp. 136–149). New York: Informa Healthcare.
Fong, C. Y., Subramanian, A., Biswas, A., et al. (2010). Derivation efficiency, cell proliferation, frozen-thaw survival, ‘stemness’ properties, and differentiation of human Wharton’s jelly stem cells: their potential for concurrent banking with cord blood for regenerative medicine purposes. Reproductive Biomedicine Online, 21, 391–401.
Angelucci, S., Marchisio, M., Giuseppe, F. D., Pierdomenico, L., Sulpizio, M., & Eleuterio, E. (2010). Proteome analysis of human Wharton’s jelly cells during in vitro expansion. Proteome Science, 8, 18–25.
Ding, D. C., Shyu, W. C., Lin, S. Z., Liu, H. W., Chiou, S. H., & Chu, T. Y. (2012). Human umbilical cord mesenchymal stem cells support non-tumorigenic expansion of human embryonic stem cells. Cell Transplantation. doi:10.3727/096368912X647199.
Kikuchi-Taura, A., Taguchi, A., Kanda, T., et al. (2012). Human umbilical cord provides a significant source of unexpanded mesenchymal stromal cells. Cytotherapy, 14, 441–450.
Lu, L. L., Liu, Y. J., Yang, S. G., et al. (2006). Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica, 91, 1017–1026.
Schugar, R. C., Chirieleison, S. M., Wescoe, K. E., et al. (2009). High harvest yield, high expansion, and phenotype stability of CD146 mesenchymal stromal cells from whole primitive human umbilical cord tissue. Journal of Biomedicine and Biotechnology, 2009, 789526.
Capelli, C., Gotti, E., Morigi, M., et al. (2011). Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate. Cytotherapy, 13, 786–801.
Bosch, J., Houben, A. P., Radke, T. F., et al. (2012). Distinct differentiation potential of ‘MSC’ derived from cord blood and umbilical cord: are cord-derived cells true mesenchymal stromal cells? Stem Cells and Development. doi:10.1089/scd.2011.0414.
Tsagias, N., Koliakos, I., Karagiannis, V., Eleftheriadou, M., & Koliakos, G. G. (2011). Isolation of mesenchymal stem cells using the total length of umbilical cord for transplantation purposes. Transfusion Medicine, 21, 253–261.
Kita, K., Gauglitz, G. G., Phan, T. T., Herndon, D. N., & Jeschke, M. G. (2010). Isolation and characterization of mesenchymal stem cells from the sub amniotic human umbilical cord lining membrane. Stem Cells and Development, 19, 491–502.
Sarugaser, R., Lickorish, D., Baksh, D., Hosseini, M. M., & Davies, J. E. (2005). Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells, 23, 220–229.
Romanov, Y. A., Svintsitskaya, V. A., & Smirnov, V. N. (2003). Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells, 21, 105–110.
Watt, S. M., Su, C. C., & Chan, J. Y. (2010). The therapeutic potential of stem cells in umbilical cord and umbilical cord blood. Journal of Medical Sciences, 30, 177–187.
Nanaev, A. K., Kohnen, G., Milovanov, A. P., Domogatsky, S. P., & Kaufmann, P. (1997). Stromal differentaition and architecture of the human umbilical cord. Placenta, 18, 53–64.
Ishige, I., Nagamura-Inoue, T., Honda, M. J., et al. (2009). Comparison of mesenchymal stem cells derived from arterial, venous and Whartons’ jelly explants of human umbilical cord. International Journal of Hematology, 90, 261–269.
Mareschi, K., Biasin, E., Piacibello, W., Aglietta, M., Madon, E., & Fagioli, F. (2001). Isolation of human mesenchymal stem cells: bone marrow versus umbilical cord blood. Haematologica, 86, 1099–1100.
Wexler, S. A., Donaldson, C., Denning-Kendall, P., Rice, C., Bradley, B., & Hows, J. M. (2003). Adult bone marrow is a rich source of human mesenchymal stem cells but umbilical cord and mobilized blood adult blood are not. British Journal of Haematology, 121, 368–374.
Lee, O. K., Kuo, T. K., Chen, W. M., Lee, K. D., Hsieh, S. L., & Chen, T. H. (2004). Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood, 103, 1669–1675.
Musina, R. A., Bekchanova, E. S., Belyavskii, A. V., Grinenko, T. S., & Sukhikh, G. T. (2007). Umbilical cord blood mesenchymal stem cells. Bulletin of Experimental Biology and Medicine, 143, 127–131.
Secco, M., Zucconi, E., Vieira, N. M., et al. (2008). Multipotent stem cells from umbilical cord: cord is richer than blood. Stem Cells, 26, 146–150.
Hass, R., Kasper, C., Bohm, S., & Jacobs, R. (2011). Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Communication and Signaling, 9, 1–14.
La Rocca, G., Anzalone, R., Corrao, S., et al. (2009). Isolation and characterization of OCT4+/HLA-G + mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers. Histochemistry and Cell Biology, 131, 267–282.
Anzalone, R., Lo Iacono, M., Corrao, S., et al. (2010). New emerging potentials for human Wharton’s jelly mesenchymal stem cells; immunological features and hepatocyte-like differentiative capacity. Stem Cells and Development, 19, 423–438.
La Rocca, G. (2011). Connecting the dots: the promises of Wharton’s jelly mesenchymal stem cells for tissue repair and regeneration. Open Tissue Engineering and Regenerative Medicine Journal, 4, 3–5.
Wang, L., Ott, L., Seshareddy, K., Weiss, M., & Detamore, M. S. (2011). Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells. Future Medicine, 6, 95–109.
Lutjimeier, B., Troyer, D. L., & Weiss, M. L. (2010). Wharton’s jelly-derived mesenchymal stromal cells. In C. L. Cetrulo, K. J. Cetrulo, & C. L. Cetrulo Jr. (Eds.), Perinatal stem cells (pp. 79–97). NJ: Wiley.
Troyer, D. L., & Weiss, M. L. (2008). Concise review: Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells, 26, 591–599.
Prasanna, S. J., & Jahnavi, V. S. (2011). Wharton’s jelly mesenchymal stem cells as off-the-shelf cellular therapeutics: a closer look into their regenerative and immunomodulatory properties. Open Tissue Engineering and Regenerative Medicine Journal, 4, 28–38.
Karahuseyinoglu, S., Cinar, O., Kilic, E., et al. (2007). Biology of stem cells in human umbilical cord stroma: In situ and in vitro surveys. Stem Cells, 25, 319–331.
Wang, X. Y., Lan, Y., He, W. Y., et al. (2008). Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood, 111, 2436–2443.
Dominici, M., Le Blanc, K., Mueller, I., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317.
Taghizadeh, R. R., Cetrulo, K. J., & Cetrulo, C. L. (2011). Wharton’s jelly stem cells: future clinical applications. Placenta, 32, S311–S315.
Meyer, T., Pfeifroth, A., & Hocht, B. (2008). Isolation, and characterization of mesenchymal stem cells in Wharton’s jelly of the human umbilical cord: potent cells for cell-based therapies in paediatric surgery? European Surgery, 40, 239–244.
Fong, C. Y., Gauthaman, K., Cheyyatraivendran, S., Lin, H. D., Biswas, A., & Bongso, A. (2012). Human umbilical cord Wharton’s jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo. Journal of Cellular Biochemistry, 113, 658–668.
Gauthaman, K., Fong, C. Y., Cheyyatraivendran, S., Biswas, A., Choolani, M., & Bongso, A. (2012). Human umbilical cord Wharton’s jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro. Journal of Cellular Biochemistry, 113, 2027–2039.
Huang, Y. C., Parolini, O., La Rocca, G., & Deng, L. (2012). Umbilical cord versus bone marrow derived mesenchymal stromal cells. Stem Cells and Development, 21, 2900–2903.
Can, A., & Karahuseyinoglu, S. (2007). Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells, 25, 2886–2895.
Weiss, M. L., Anderson, C., Medicetty, S., et al. (2008). Immune properties of human umbilical cord Wharton’s jelly-derived cells. Stem Cells, 26, 2865–2874.
Tipnis, S., Viswanathan, C., & Majumdar, A. S. (2010). Immunosuppressive properties of human umbilical cord-derived mesenchymal stem cells: role of B7-H1 and IDO. Immunology and Cell Biology, 88, 795–806.
Fan, C. G., Zhang, Q., & Zhou, J. (2011). Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Reviews and Reports, 7, 195–207.
Gauthaman, K., Venugopal, J. R., Fong, C. Y., Biswas, A., Ramakrishna, S., & Bongso, A. (2011). Osteogenic differentiation of human Wharton’s jelly stem cells on nanofibrous substrates in vitro. Tissue Engineering. Part A, 17, 71–81.
Fong, C. Y., Subramanian, A., Gauthaman, K., et al. (2012). Human umbilical cord Wharton’s jelly stem cells undergo enhanced chondrogenic differentiation when grown on nanofibrous scaffolds and in a sequential two-stage culture medium environment. Stem Cell Reviews and Reports, 8, 195–209.
Vidal, M. A., Walker, N. J., Napoli, E., & Borjesson, D. L. (2012). Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue and umbilical cord tissue. Stem Cells and Development, 21, 273–283.
La Rocca, G., Anzalone, R., & Farina, F. (2009). The expression of CD68 in human umbilical cord mesenchymal stem cells: new evidences of presence in non-myeloid cell types. Scandinavian Journal of Immunology, 70, 161–162.
Fong, C. Y., Chak, L. L., Biswas, A., et al. (2011). Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Reviews and Reports, 7, 1–16.
Carlin, R., Davis, D., Weiss, M., Schultz, B., & Troyer, D. (2006). Expression of early transcription factors Oct-4, Sox-2 and nanog by porcine umbilical cord (PUC) matrix cells. Reproductive Biology and Endocrinology, 4, 1–13.
Nekanti, U., Rao, V. B., Bahirvani, A. G., Jan, M., Totey, S., & Ta, M. (2010). Long-term expansion and pluripotent marker array analysis of Whartons jelly-derived mesenchymal stem cells. Stem Cells and Development, 19, 117–130.
Hoynowski, S. M., Fry, M. M., Gardner, B. M., et al. (2007). Charaterization and differentiation of equine umbilical cord derived matrix cells. Biochemical and Biophysical Research Communications, 362, 347–353.
Gauthaman, K., Fong, C. Y., Suganya, C. A., et al. (2012). Extra-embryonic human Wharton’s jelly stem cells do not induce tumorigenesis, unlike human embryonic stem cells. Reproductive Biomedicine Online, 24, 235–246.
Wang, Y., Han, Z. B., Ma, J., et al. (2012). A toxicity study of multiple-administration human umbilical cord mesenchymal stem cells in cynomolgus monkeys. Stem Cells and Development, 21, 1401–1408.
Fong, C. Y. (1993). Human tubal cell coculture: In vitro cell behaviour and use of conditioned medium for embryonic support. MSc. Thesis. Singapore: National University of Singapore.
Fu, Y. S., Shih, Y. T., Cheng, Y. C., & Min, M. Y. (2004). Transformation of human umbilical mesenchymal cells into neurons in vitro. Journal of Biomedical Science, 11, 652–660.
Garzón, I., Pérez-Köhler, B., Garrido-Gómez, J., et al. (2012). Evaluation of the cell viability of human Wharton’s jelly stem cells for use in cell therapy. Tissue Engineering. Part C, Methods, 18, 408–419.
Ma, L., Feng, X. Y., Cui, B. L., et al. (2005). Human umbilical cord Wharton’s Jelly-derived mesenchymal stem cells differentiation into nerve-like cells. Chinese Medical Journal, 118, 1987–1993.
Mitchell, K. E., Weiss, M. L., Mitchell, B. M., et al. (2003). Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells, 21, 50–60.
Conconi, M. T., Burra, P., Di, L. R., Calore, C., et al. (2006). CD 105 (+) cells from Wharton’s Jelly show in vitro and in vivo myogenic differentiative potential. International Journal of Molecular Medicine, 18, 1089–1096.
Wu, K. H., Zhou, B., Lu, S. H., et al. (2007). In vitro and in vivo differentiation of human umbilical cord derived stem cells into endothelial cells. Journal of Cellular Biochemistry, 100, 608–616.
Chao, K. C., Chao, K. F., Fu, Y. S., & Liu, S. H. (2008). Islet-like clusters derived from mesenchymal stem cells in Wharton’s jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One, e1451, 1–9.
Anzalone, R., Lo Lacono, M., Loria, T., et al. (2011). Wharton’s jelly mesenchymal stem cells as candidates for beta cells regeneration: Extending the differentiative and immunomodulatory benefits of adult mesenchymal stem cells for the treatment of Type 1 diabetes. Stem Cell Reviews and Reports, 7, 342–363.
Medicetty, S., Bledsoe, A. R., Fahrenholtz, C. B., Troyer, D., & Weiss, M. L. (2004). Transplantation of pig stem cells into rat brain: proliferation during the first 8 weeks. Experimental Neurology, 190, 32–41.
Yang, D., Zhang, Z., Oldenberg, M., Ayala, M., & Zhang, S. C. (2008). Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in Parkinsonian rats. Stem Cells, 26, 55–63.
Deuse, T., Stubbendorff, M., Tang-Quan, K., et al. (2011). Immunogenecity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplantation, 20, 655–667.
Prasanna, S. J., Gopalakrishnan, D., Shankar, S. R., & Vasandan, A. B. (2010). Pro-inflammatory cytokines, IFNγ and TNFα, influence immune properties of human bone marrow and Wharton’s jelly mesenchymal stem cells differentially. PLoS One, 5, e9016.
De Coppi, P., Bartsch, G., Jr., Siddiqui, M. M., et al. (2007). Isolation of amniotic stem cell lines with potential for therapy. Nature Biotechnology, 25, 100–106.
Illancheran, S., Moodley, Y., & Manuelpillai, U. (2009). Human fetal membranes: a source of stem cells for tissue regeneration and repair? Placenta, 3, 2–10.
Rachkatla, R. S., Marini, F., Weiss, M. L., Tamura, M., & Troyer, D. (2007). Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors. Cancer Gene Therapy, 14, 828–835.
Ayuzawa, R., Doi, C., Rachakatla, R. S., et al. (2009). Naïve human umbilical cord matrix derived stem cells significantly attenuate growth of human breast cancer cells in vitro and in vivo. Cancer Letters, 280, 31–37.
Ganta, C., Chiyo, D., Ayuzawa, R., et al. (2009). Rat umbilical cord stem cells completely abolish rat mammary carcinomas with no evidence of metastasis or recurrence 100 days post-tumor cell inoculation. Cancer Research, 69, 1815–1820.
Maurya, D. K., Doi, C., Kawabata, A., et al. (2010). Therapy with un-engineered naïve rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma. BMC Cancer, 10, 590–601.
Sun, B., Yu, K. R., Bhandari, D. R., Jung, J. W., Kang, S. K., & Kang, K. S. (2010). Human umbilical cord blood mesenchymal stem cell-derived extracellular matrix prohibits metastatic cancer cell MDA-MB-231 proliferation. Cancer Letters, 296, 178–185.
Chao, K. C., Yang, H. T., & Chen, M. W. (2011). Human umbilical cord mesenchymal stem cells suppress breast cancer tumorogenesis through direct cell-cell contact and internalization. Journal of Cellular and Molecular Medicine, 16, 1803–1815.
Ma, Y., Hao, X., Zhang, S., & Zhang, J. (2012). The in vitro and in vivo effects of human umbilical cord mesenchymal stem cells on the growth of breast cancer cells. Breast Cancer Research and Treatment, 133, 473–485.
Chamberlain, G., Fox, J., Ashton, B., & Middleton, J. (2007). Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells, 25, 2739–2749.
Håkelien, A. M., & Collas, P. (2002). Novel approaches to transdifferentiation. Cloning and Stem Cells, 4, 379–387.
Taranger, C. K., Noer, A., Sørensen, A. L., Håkelien, A. M., Boquest, A. C., & Collas, P. (2005). Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Molecular Biology of the Cell, 16, 5719–5735.
Friedman, R., Betancur, M., Boissel, L., Tuncer, H., Cetrulo, C., & Klingemann, H. (2007). Umbilical cord mesenchymal stem cells: adjuvants for human cell transplantation. Biology of Blood and Bone Marrow Transplantation, 13, 1477–1486.
Bakhshi, T., Zabriskie, R. C., Bodies, K., Ramin, S., Laura, A., & Paganessi, L. A. (2008). Mesenchymal stem cells from the Wharton’s jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture. Transfusion, 48, 2638–2644.
Matsuzuka, T., Rachakatla, R. S., Doi, C., et al. (2010). Human umbilical cord matrix-derived stem cells expressing interferon-β gene significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice. Lung Cancer, 70, 28–36.
Subramanian, A., Gan, S. U., Ngo, K. S., et al. (2012). Human umbilical cord Wharton’s jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells. Journal of Cellular Biochemistry, 113, 1886–1895.
Magin, A. S., Korfer, N. R., Partenheimer, H., Iange, C., Zander, A., & Noll, T. (2009). Primary cells as feeder cells for coculture expansion of human hematopoietic stem cells from umbilical cord blood-a comparative study. Stem Cells and Development, 18, 173–186.
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The authors’ studies reported in this review were carried out under grant numbers R-174-000-131-213, R-174-000-122-112 and R-174-000-129-112. The financial support from the National Medical Research Council (NMRC) Singapore and the Academic Research Fund (AcRF) for these grants is gratefully acknowledged.
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Bongso, A., Fong, CY. The Therapeutic Potential, Challenges and Future Clinical Directions of Stem Cells from the Wharton’s Jelly of the Human Umbilical Cord. Stem Cell Rev and Rep 9, 226–240 (2013). https://doi.org/10.1007/s12015-012-9418-z
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DOI: https://doi.org/10.1007/s12015-012-9418-z