Human iPSC-MSC-Derived Xenografts Modulate Immune Responses by Inhibiting the Cleavage of Caspases.

Autor: Li CL; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China., Leng Y; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Zhao B; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Gao C; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Du FF; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Jin N; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Lian QZ; Department of Ophthalmology, and Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, People's Republic of China., Xu SY; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Yan GL; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Xia JJ; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Zhuang GH; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China., Fu QL; Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China., Qi ZQ; Organ Transplantation Institute, Medical College, Xiamen University, Xiamen, Fujian, People's Republic of China.; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, People's Republic of China.; Xiamen Key Laboratory of Regenerative Medicine, Xiamen, Fujian, People's Republic of China.
Jazyk: angličtina
Zdroj: Stem cells (Dayton, Ohio) [Stem Cells] 2017 Jul; Vol. 35 (7), pp. 1719-1732. Date of Electronic Publication: 2017 May 18.
DOI: 10.1002/stem.2638
Abstrakt: Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear. We established an iPSC-MSC-transplanted host versus graft reaction mouse model using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17 phenotypes and their cytokines were investigated in vivo and in vitro. The role of caspases and the soluble factors involved in the effects of MSCs were examined. We found that iPSC-MSC grafts led to more cell survival and less infiltration of inflammatory cells in mice. iPSC-MSC transplantation inhibited T cell proliferation, decreased Th1 and Th2 phenotypes and cytokines, upregulated Th17 and Treg subsets. Moreover, iPSC-MSCs inhibited the cleavage of caspases 3 and 8 and inhibition of caspases downregulated Th1, Th2 responses and upregulated Th17, Treg responses. Soluble factors were determined using protein array and TGF-β1/2/3, IL-10, and MCP-1 were found to be highly expressed in iPSC-MSCs. The administration of the soluble factors decreased Th1/2 response, upregulated Treg response and inhibited the cleavage of caspases. Our results demonstrate that iPSC-MSCs regulate T cell responses as a result of a combined action of the above soluble factors secreted by iPSC-MSCs. These factors suppress T cell responses by inhibiting the cleavage of caspases. These data provide a novel immunomodulatory mechanism for the underlying iPSC-MSC-based immunomodulatory effects on T cell responses. Stem Cells 2017;35:1719-1732.
(© 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)
Databáze: MEDLINE
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