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

2017, Transplantation Proceedings

Bone marrowemesenchymal 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 antiinflammatory 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 þ MSCs group) or pancreatic islets only (islet group). Compared to the islet group, islet þ MSCs had a lower expression of inflammatory markers, such as, tumor necrosis factore a (13.40 AE 0.57 vs. 9.90 AE 0.12, P ¼ .01), monocyte chemoattractant protein 1 (51.30 AE 6.80 vs. 9.00 AE 1.80, P ¼ .01), and interleukin 1b (IL-1b) (16.2 AE 1.65 vs. 6.80 AE 1.00, P ¼ .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 AE 1.96 vs. 2.80 AE 0.20, P ¼ .004), IL-10 (188.40 AE 4.60 vs. 4.55 AE 0.12, P ¼ .0001), and forkhead box P3 (34.20 AE 1.3 vs. 1.30 AE 0.2, P ¼ .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. MATERIALS AND METHODS Animals All animal experiments were approved by the local Ethics Committee of Pontifical Catholic University (Parana, Brazil), and were performed in accordance with the national guidelines for care and Supported by CNPq (Processo N 0 473473/2007-0), Fundação Araucária (Convênio no. 297/2007; Protocolo no. 9209) e Fundação Pró-Renal.