[Allogenic BMSCs reverse chimerism inducing the tolerance of xeno-skin graft in mouse model].

Sichuan Da Xue Xue Bao Yi Xue Ban

Key Laboratory of Transplant Engineering and Immunology, Ministry of Healthy, West China Hospital, Sichuan University, Chengdu 610041, China.

Published: March 2013

Objective: To investigate the feasibility of bone marrow mesenchymal stem cells (BMSCs) in inducing immune tolerance and to establish the mouse model of reverse chimerism in xeno-skin transplantation.

Methods: The mouse model of bone marrow-chimerism was established with immuncompromised BALB/C-nu/nu female mice by receiving the transplantation of BMSCs from green fluorescent protein (GFP)-C57BL/10 male mice, the optimized chimeric time was identified by RT-PCR testing of SRY gene and immunohistochemistry measurement of GFP expression. In the experiment group, GFP-C57BL/10 male mice received the transplantation of the skin from immuncompromised BALB/C-nu/nu female mice with BMSCs bone marrow-chimerism. In the rejection group, GFP-C57BL/10 male mice received the transplantation of the skin from immuncompromised BALB/C-nu/nu female mice without BMSCs bone marrow-chimerism. In the control group, allo-transplantation of skin was performed in GFP-C57BL/10 male mice. Histological study was performed to investigate the survival rate and angiogenesis of the transplanted skin.

Results: The bone marrow chimeric model was established, the expressions of SRY gene and GFP protein reached the highest level at four weeks (1.22 +/- 0.10; 458.0 +/- 3.4) post-transplanted with BMSCs (10(6)), which was significantly different in comparison with those at one week, two weeks and six weeks posttransplantation(P < 0.05). Four-weeks after transplantation was further confirmed as the optimized chimeric time. The mean survival time of donor skin graft > 14 d in the experimental group, while it only was 5 d in the rejection group.

Conclusion: The bone marrow-chimerism can be formed in the recipient by donor BMSCs transplantation, which can further induce tolerance of mice xeno-skin transplantation by reverse chimerism.

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