A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome

Abstract

Type 1 Diabetes (T1D) is a chronic autoimmune disease characterized by a gradual destruction of insulin-producing β-cells in the endocrine pancreas due to innate and specific immune responses, leading to impaired glucose homeostasis. T1D patients usually require regular insulin injections after meals to maintain normal serum glucose levels. In severe cases, pancreas or Langerhans islet transplantation can assist in reaching a sufficient β-mass to normalize glucose homeostasis. The latter procedure is limited because of low donor availability, high islet loss, and immune rejection. There is still a need to develop new technologies to improve islet survival and implantation and to keep the islets functional. Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells with high plasticity that can support human pancreatic islet function both in vitro and in vivo and islet co-transplantation with MSCs is more effective than islet transplantation alone in attenuating diabetes progression. The beneficial effect of MSCs on islet function is due to a combined effect on angiogenesis, suppression of immune responses, and secretion of growth factors essential for islet survival and function. In this review, various aspects of MSCs related to islet function and diabetes are described.

Evaluating the efficacy of mesenchymal stem cells for diabetic neuropathy: A systematic review and meta-analysis of preclinical studies

“…After MSC administration, significant decreases in blood glucose were observed in five studies, but rodents in these treatment arms still met the diagnostic criteria for diabetes. MSCs may exert their beneficial effects both by differentiating into pancreatic islet cells and by secreting an array of growth factors that can rejuvenate pancreatic islet cells, such as insulin-like growth factor 1 (IGF-1), pancreatic and duodenal homeobox 1 (PDX-1), and glucagon-like peptide-1 (GLP-1) ( Sionov and Ahdut-HaCohen, 2023 ). Despite these outcomes, MSCs were unable to normalize the blood glucose levels in diabetic rodents, suggesting that their ability to regulate blood glucose may be not as robust as their neurotrophic and angiogenesis functions.…”