Xenograft of microencapsulated Sertoli cells for the cell therapy of type 2 diabetes mellitus in spontaneously diabetic nonhuman primates: preliminary data

Transplant Proc. 2014 Jul-Aug;46(6):1999-2001. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / metabolism
  • Hypoglycemic Agents / therapeutic use
  • Injections, Intraperitoneal
  • Insulin / therapeutic use
  • Insulin Resistance / physiology
  • Macaca mulatta
  • Male
  • Obesity / complications
  • Sertoli Cells / transplantation*
  • Swine
  • Transplantation, Heterologous*

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin