Xenograft of Microencapsulated Sertoli Cells for the Cell Therapy of Type 2 Diabetes Mellitus in Spontaneously Diabetic Nonhuman Primates: Preliminary Data |
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Authors: | G. Luca D.F. Cameron I. Arato F. Mancuso E.H. Linden M. Calvitti G. Falabella K. Szekeres M. Bodo G. Ricci B.C. Hansen R. Calafiore |
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Affiliation: | 1. Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy;2. Department of Internal Medicine, University of South Florida, Tampa, FL;3. Department of Internal Medicine, University of Perugia, Perugia, Italy |
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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. |
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