Abstract
Mesenchymal stem cells (MSCs) derived from bone marrow are feasible for the exertion of a powerful immunoregulatory effect and thus shall hold a curative potency in T lymphocyte-dependent pathologies. This current article is intended to describe the method to investigate that MSCs might take advantage of regulation in graft-versus-host disease (GvHD), a major etiology of attack rate and lethality post allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were isolated from Lewis rat bone morrow and cultured for 4 weeks. The purification of enriched conventional MSCs and macrophages was achieved by autoMACS. Using the limiting dilution method, MSCs were cloned and then expanded until more than 6 months. The cultured MSCs showed a typical spindle-shaped morphology and immunophenotypes, lack of CD45 and CD11b/c expression. MSCs are also known for their ability to differentiate into adipocytes. MSCs, like macrophages, exhibit the immunomodulatory propensity to inhibit T lymphocyte proliferation. Following the adoptive transfer, MSCs regulate systemic Lewis to (Lewis × DA) F1 rat GvHD. Meanwhile, the cloned MSCs surprisingly enhanced T cell proliferation in vitro and yielded no clinical benefit in regard to the incidence or severity of GvHD. This is in contradistinction to the immunosuppressive activities of MSCs as conventionally described. Hence, this rat GvHD model treated with MSCs has shown intriguing differences in the regulatory effects of lymphocyte proliferation and GvHD repression between short-term cultured conventional MSCs and cloned MSCs.
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Acknowledgement
This study was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid 20390349, 21659310, 2109739) and the National Center for Child Health and Development (22-10). National Natural Science Foundation of China (81370230), the Major International (Regional) Joint Research Project (2008 DFA31140, 2010 DFA32660).
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Fujino, M., Zhu, P., Kitazawa, Y., Chen, JM., Zhuang, J., Li, XK. (2014). Mesenchymal Stem Cells Attenuate Rat Graft-Versus-Host Disease. In: Christ, B., Oerlecke, J., Stock, P. (eds) Animal Models for Stem Cell Therapy. Methods in Molecular Biology, vol 1213. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1453-1_28
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DOI: https://doi.org/10.1007/978-1-4939-1453-1_28
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