Modulation of Alloimmune Responses by Interleukin-10 Prevents Rejection of Implanted Allogeneic Smooth Muscle Cells and Restores Postinfarction Ventricular Function

Cell Transplantation

Article

Jim Hu¹  Shu-Hong Li²  Ren-Ke Li²  Anton Mihic²  Xi-Ping Huang²  Jun Wu²  Sanjiv Dhingra²  Jian Guo²  Richard D. Weisel² 

[1] Department of Laboratory Medicine and Pathobiology (Pediatrics), University of Toronto and Physiology and Experimental Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada;Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network and Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada;

关键词: Cell therapy;    Myocardial infarction;    Cardiac regeneration;    Immune rejection;    Interleukin-10 (IL-10);   

DOI  :  10.3727/096368914X681036

 received in 2013-11-25, accepted in 2014-04-09,  发布年份 2015

来源: Sage Journals

【 摘 要 】

Interleukin-10 (IL-10) gene transduction into allogeneic smooth muscle cells (SMCs) was evaluated to improve the long-term benefits of allogeneic cell transplantation into infarcted myocardium. Allogeneic cells, including SMCs, have been demonstrated to restore cardiac function and repair the infarcted myocardium, but late rejection of the transplanted cells by the host immune system may reverse the benefits of cell therapy. In a rat myocardial infarction model, three groups of rats were injected with either unmodified autologous, unmodified allogeneic, or allogeneic + IL-10 SMCs into the infarct region. Three weeks later, most of the allogeneic cells were rejected, whereas autologous cells were engrafted in the myocardium. IL-10 gene transduction of the allogeneic SMCs significantly improved the cell survival. To understand the mechanism of this improved survival, we evaluated the host immune responses against the SMCs. Allogeneic SMCs expressing IL-10 decreased leukocyte-mediated cytotoxicity in coculture, decreased the number of cytotoxic CD8+ T-cells, and increased the number of CD4+CD25+ regulatory T-cells in vitro and in vivo. Furthermore, IL-10 prevented the production of antidonor antibodies by the recipients against the allogeneic SMCs. Transplantation of unmodified autologous SMCs, but not unmodified allogeneic SMCs, significantly improved fractional shortening and left ventricular dimensions compared to the media-injected control group. However, IL-10 gene-enhanced allogeneic SMCs improved ventricular function, increased wall thickness, and decreased scar length in association with their enhanced survival. We conclude that IL-10 gene-enhanced cell therapy with allogeneic SMCs prevents detrimental alloimmune responses in the recipient, thereby increasing the survival of transplanted allogeneic SMCs and more effectively restoring cardiac function.

【 授权许可】

Unknown   
© 2015 Cognizant Comm. Corp.

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