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Local Delivery of Adipose-Derived Stem Cells Promotes Allograft Survival and Durable Tolerance in Vascularized Composite Allotransplantation
Hengyun Sun, Jingjing Li, Wensheng Zhang, Zhongchen Wang, J. Peter Rubin, Mario Solari, Lauren Kokai
Research center training program
2019-02-15
Presenter: Hengyun Sun
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: Lauren Kokai
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background: Culture expanded adipose stem cells (ASCs) have immunomodulatory and anti-inflammatory activities and when delivered systemically, ASCs have demonstrated promise in inducing transient tolerance in VCA models. We hypothesize that local delivery of ASCs will improve survival outcomes compared to systemic delivery. The purpose of this study was to compare graft rejection after VCA with systemic, local and contralateral ASC delivery and investigate potential immunosuppressive mechanisms of action.
Methods: In Vitro. Passage three donor-derived ASCs were exposed to IFNg and TNFa for 2h, 4h, 6h and 24h. Expression of immunomodulatory relative genes were examined with real-time PCR. In Vivo. Hindlimbs of male Brown Norway donors were grafted onto male Lewis (LEW), a full MHC mismatch. Immunosuppressants were delivered up to 21 days. Donor ASCs (1*106 cells/rat) were injected locally or systemically at postoperative day 1. Survival time was compared between treatment groups.
Results: In vitro, ASCs secreted high levels of anti-inflammatory factors such as PGE2, IDO and iNOS after 6-24 hours exposure to IFNg and/or TNFa. In vivo, local-ASC delivery significantly extended long-term (>130 days) allograft survival compared with systemically treated rats (median survival time was 44 days).
Conclusions: Local delivery of ASC significantly prolonged allograft survival time and reduced immunosuppressive burden. Secretion of IDO could play a vital role in the mechanism of action for ASC-mediated immunosuppression in VCA. Future studies will investigate conformational changes in cell surface proteins that induce innate immunity, inflammation and graft tissue damage in VCA grafts that are also ameliorated with ASC therapy.
