Co-transplantation of Xenogeneic Bone Marrow-derived Mesenchymal Stem Cells Alleviates Rejection of Pancreatic Islets in Non-obese Diabetic Mice

摘要

Bone marrow-mesenchymal stem cells (BM-MSCs) have generated a great perspective in the field of regenerative medicine, and also in the treatment of inflammatory and autoimmune diseases in the past decade due to their immunomodulatory and anti-inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs and pancreatic islets co-transplantation obtained from Wistar rats in preventing rejection or inducing tolerance to islet transplantation in non-obese diabetic mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group). Compared to the islet group, islet + MSCs had a lower expression of inflammatory markers, such as, tumor necrosis factor-alpha (13.40 +/- 0.57 vs. 9.90 +/- 0.12, P =.01), monocyte chemoattractant protein 1 (51.30 +/- 6.80 vs. 9.00 +/- 1.80, P =.01), and interleukin 1 beta (IL-1 beta) (16.2 +/- 1.65 vs. 6.80 +/- 1.00, P =.04). Comparing the expression of immune tolerance markers, it is noted that animals receiving the co-transplantation showed a significantly higher expression than the islet group of IL-4 (25.60 +/- 1.96 vs. 2.80 +/- 0.20, P =.004), IL-10 (188.40 +/- 4.60 vs. 4.55 +/- 0.12, P =.0001), and forkhead box P3 (34.20 +/- 1.3 vs. 1.30 +/- 0.2, P =.004), respectively. These results suggest an immunomodulatory action of BM-MSC in islet xenotransplantation showing that these stem cells have the potential to mitigate the early losses of grafts, due to the regulation of the inflammatory process of transplantation.