title: Xenograft of microencapsulated Sertoli cells for the cell therapy of type 2 diabetes mellitus in spontaneously diabetic nonhuman primates: preliminary data.
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.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Luca
authors.affiliation: Department of Internal Medicine, University of South Florida, Tampa, FL.
authors.forename: D F
authors.initials: DF
authors.lastname: Cameron
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Arato
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mancuso
authors.affiliation: Department of Internal Medicine, University of South Florida, Tampa, FL.
authors.forename: E H
authors.initials: EH
authors.lastname: Linden
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Calvitti
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Falabella
authors.affiliation: Department of Internal Medicine, University of South Florida, Tampa, FL.
authors.forename: K
authors.initials: K
authors.lastname: Szekeres
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bodo
authors.affiliation: Department of Internal Medicine, University of Perugia, Perugia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ricci
authors.affiliation: Department of Internal Medicine, University of South Florida, Tampa, FL.
authors.forename: B C
authors.initials: BC
authors.lastname: Hansen
authors.affiliation: Department of Internal Medicine, University of Perugia, Perugia, Italy. Electronic address: riccardo.calafiore@unipg.it.
authors.forename: R
authors.initials: R
authors.lastname: Calafiore
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000628:therapy*; D004339:Drug Compounding; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D009765:Obesity / Q000150:complications; D012708:Sertoli Cells / Q000637:transplantation*; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin