Xenograft of Microencapsulated Sertoli Cells for the Cell Therapy of Type 2 Diabetes Mellitus in Spontaneously Diabetic Nonhuman Primates: Preliminary Data

• Published in: Transplantation proceedings 2014-07, Vol.46 (6), p.1999-2001
• Main Authors: Luca, G, Cameron, D.F, Arato, I, Mancuso, F, Linden, E.H, Calvitti, M, Falabella, G, Szekeres, K, Bodo, M, Ricci, G, Hansen, B.C, Calafiore, R
• Format: Article
• Language: English
• Subjects: Animals; Cell- and Tissue-Based Therapy - methods; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - therapy; Drug Compounding; Glycated Hemoglobin A - metabolism; Hypoglycemic Agents - therapeutic use; Injections, Intraperitoneal; Insulin - therapeutic use; Insulin Resistance - physiology; Macaca mulatta; Male; Obesity - complications; Sertoli Cells - transplantation; Surgery; Swine; Transplantation, Heterologous
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2014.06.053

Abstract Insulin resistance in type 2 diabetes mellitus (T2DM) may be due to a chronic inflammation of the visceral adipose tissue (VAT) leading to local and systemic increases in proinflammatory cytokines. Microencapsulated porcine Sertoli cells (MC-pSC), by provision of immunomodulatory and trophic factors, have been successfully used to reduce such inflammation in rodent animal models of type 1 diabetes with no complications or deleterious side effects. Herein, we have begun to investigate this novel and safe therapeutic approach in the spontaneously obese nonhuman primate with spontaneous, insulin-dependent T2DM. After MC-pSC intraperitoneal injection we have evaluated, throughout a 6-month follow-up period, daily ad libitum fed glucose levels, daily exogenous insulin supplementation, biweekly body weight measurements, periodic fasting blood glucose concentrations, glycated hemoglobin (HbA1c) levels, glucose tolerance tests (GTT), and fluorescence-activated cell sorting cytometry (FACS) assessment of peripheral blood mononuclear cells. Very preliminarily, we have observed a slight reduction in fasting (FPG) and mean nonfasting (NF) plasma glucose levels. We found minimal changes, only in 1 animal, in daily exogenous insulin requirements and HbA1c levels. Flow cytometric analysis was associated with decrease in CD8+ cells only in 1 recipient with a reduction in mean regulatory T Cells (Treg), whereas interestingly, decrease of B lymphocytes was observed in both animals. These results may suggest that this novel MC-SC–based transplantation protocol might possibly impact the metabolic status of T2DM in higher mammals that are close to humans.