Background

The Edmonton protocol revived islet transplantation therapy for Type-1 Diabetic patients. However, Long-term islet function still remains a challenge. Immunosuppression used after islet transplantation contributes to graft failure. Islet transplantation requires alternative approaches to improve immunosuppression. We hypothesized that remnant tissue after islet isolation could be used to recover MSCs. The purpose of this study is to determine if pancreas-derived MSCs have the capacity to be used as immunosuppression during islet co-transplantation.

Methods

Pancreatic tissue from COBE bag remnants was cultured and plastic-adherent cells were isolated and identified as MSCs by morphology and surface marker expression. MSCs (2×10^5 cells) were cultured. Human T cells were stained with CFSE, stimulated with CD3/CD28 beads and cultured with or without MSCs for 5 days. Cells were co-cultured in direct contact or separated by a transwell membrane. T Cells separated from beads were analyzed by flow cytometry for proliferation.

Results

The culture of islet isolation remnant tissue resulted in plastic-adherent cells of fibroblast-like morphology after 3 passages. Flow cytometry showed homogeneous expression of CD90, CD73, CD29, CD105, and negative expression of CD14, CD34, and CD45 as classically characterized markers for MSC. Co-culture of pancreas-derived MSCs and human T cells stimulated with CD3/CD28 beads resulted in suppression of T cell proliferation in vitro. Moreover, Cell-cell contact of MSCs with activated T cells was required for effective suppression of T cell proliferation. Conclusion

Pancreas-derived MSCs significantly inhibited T cell proliferation demonstrating immunosuppressive properties by direct contact with activated T cells. Co-transplantation models should be further studied to assess the true potential of an MSC-derived immunosuppressive strategy in allogenic islet cell transplants.

CITATION INFORMATION: Kanak M, Kunnathodi F, Levy M, Lawrence M, Naziruddin B. Immunosuppressive Role of Pancreas Derived Mesenchymal Stem Cells. Am J Transplant. 2017;17 (suppl 3).

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