Background. Recently rodent and porcine bone marrow stromal cells (MSCs) have been reported to be uniquely immune tolerant. In order to confirm these findings in human cells, we tested the hypothesis that human MSCs are also immune tolerant, such that they can be useful as "universal donor cells" for myocardial regenerative therapy. / Methods. Immunocompetent female rats underwent left coronary ligations (n=90). They were randomized into 3 groups. In Group I, lac-Z labeled male human MSCs were implanted into the peri-infarcted area. In Group II and III isogenic rat MSCs or culture medium were injected respectively. Echocardiography was carried out to assess cardiac function, and the specimens were examined serially for up to 8 weeks with immunohistochemistry, FISH and PCR to examine MSCs survival and differentiation. / Results. Human MSCs were found to survive within the rat myocardium without immunosuppression. This was confirmed by PCR and FISH test. No cellular infiltration characteristic of immune rejection was noted. Some of these cells appeared to express cardiomyocyte-specific markers such as troponin-Ic and connexin-43. Furthermore, the implanted MSCs significantly contributed to the improvement in ventricular function and attenuated LV remodeling. / Conclusions. Human MSC survived within this xenogeneic environment, and contributed to the improvement in cardiac function. Our findings support the feasibility of using these cells as "universal donor cells" for xeno- or allo-geneic cell therapy, as they can be tested, prepared and stored well in advance for urgent use. Allogeneic MSCs from healthy donors may be particularly useful for severely ill or elderly patients whose own MSCs could be dysfunctional. / Plusieurs études ont récemment démontré la tolérance immunologiquedes cellules souches stromales (CSS) issues de rongeurs et de porcinés. Pour confirmer cesrésultats chez les cellules humaines, l'étude actuelle évalue l'effet des CSS humaines sur larégénération du myocarde chez des rats immunocompétents et étudie la possibilité d'utiliserces CSS comme « donatrices universelles» à la suite d'un infarctus.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101837 |
| Date | January 2007 |
| Creators | Atoui, Rony R. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Surgical Research.) |
| Rights | © Rony R. Atoui, 2007 |
| Relation | alephsysno: 002652547, proquestno: AAIMR38386, Theses scanned by UMI/ProQuest. |
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