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Local Delivery of Adipose-Derived Mesenchymal Stem Cells Promote Allograft Survival and Immunomodulation in Vascularized Composite Allotransplantation (VCA)
Jingjing Li, Wensheng Zhang, Yong Wang, Chiaki Komatsu, Moriah Johngrass, Lauren Kokai, Kacey Marra, Peter J Rubin, Kia Washington, Mario Solari
Department of Plastic Surgery, University of Pittsburgh
2018-02-01
Presenter: Jingjing Li
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting.
Director Name: Mario Soalri
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Purpose: Adipose-derived mesenchymal stem cells (ASC) are considered to be ideal for cell-based immunotherapies due to their good accessibility, high yield, and potential immunosuppressive capacity. Our previous study has demonstrated that systemically-administered donor-derived ASC promoted long-term survival in a rat model of VCA. In this study, we investigated the effects of local vs. systemic ASC delivery on VCA allograft survival and alloimmune responses.
Methods: Lewis rats received hind-limb transplants from BN rats and were administered donor-derived ASC (1×106cells/animal) systemically (intravenous) or locally (hypodermis of allograft) at postoperative day 1, combined with anti-lymphocyte serum (day -4 and +1) and FK506 (day 0-21). The changes in chimerism and immune cells in recipients' peripheral blood were assessed by flow cytometry. The immunosuppressive function of ASC was tested by mixed lymphocyte reaction (MLR) assays.
Results: All rats with local-ASC treatment achieved long-term (>130 day) allograft survival, while allograft survival time was 44 days in systemic-ASC group. Donor cell chimerism was detected in all ASC-treated recipients at day 8 posttransplantation. Levels of CD4+CD25+Foxp3+ cells and CD4+IL-10+ cells in local-ASC group were elevated and maintained through 8 weeks after withdrawal of FK506, compared with systemic-ASC group, while CD4+IL-17+ cells and CD4+IFN-r+ cells were reduced in both local- and systemic-ASC groups compared to naïve rats. In vitro study showed that ASC inhibited T-cell proliferation in a cell contact–independent way.
Conclusions: These results indicate that local delivery of ASC significantly prolong allograft survival, exert beneficial effects on modulating alloimmune response and T-cell regulation in VCA.
