Abstract
ABSTRACTHuman umbilical cord matrix-derived stem cells (uMSCs), owing to their cellular and procurement advantages compared with mesenchymal stem cells derived from other tissue sources, are in clinical trials to treat type 1 (T1D) and type 2 diabetes (T2D). However, the therapeutic basis remains to be fully understood. The immunomodulatory property of uMSCs could explain the use in treating T1D; however, the mere immune modulation might not be sufficient to support the use in T2D. We thus tested whether uMSCs could exert direct trophic effects on β-cells. Infusion of uMSCs into chemically induced diabetic rats prevented hyperglycemic progression with a parallel preservation of islet size and cellularity, demonstrating the protective effect of uMSCs on β-cells. Mechanistic analyses revealed that uMSCs engrafted long-term in the injured pancreas and the engraftment markedly activated the pancreatic PI3K pathway and its downstream anti-apoptotic machinery. The pro-survival pathway activation was associated with the expression and secretion of β-cell growth factors by uMSCs, among which insulin-like growth factor 1 (IGF1) was highly abundant. To establish the causal relationship between the uMSC-secreted factors and β-cell survival, isolated rat islets were co-cultured with uMSCs in the transwell system. Co-culturing improved the islet viability and insulin secretion. Furthermore, reduction of uMSC-secreted IGF1 via siRNA knockdown diminished the protective effects on islets in the co-culture. Thus, our data support a model whereby uMSCs exert trophic effects on islets by secreting β-cell growth factors such as IGF1. The study reveals a novel therapeutic role of uMSCs and suggests that multiple mechanisms are employed by uMSCs to treat diabetes.
Highlights
Diabetes is one of the most prevailing diseases worldwide
The diabetic rat model was established by a single-dose injection of streptozotocin (STZ) that destroys -cells (Lenzen, 2008)
Because of high systemic levels of the growth factors, especially umbilical cord matrix-derived stem cells (uMSCs)-secreted insulin-like growth factor 1 (IGF1), we evaluated the impact on the liver pAkt and pERK1/2
Summary
Diabetes is one of the most prevailing diseases worldwide. It is characterized by hyperglycemia resulting from an absolute or relative insulin deficiency. The chronic hyperglycemia of diabetes is associated with disabling damages of various organs such as the eye, kidneys, nerves, and heart. All T1D and one-third of T2D are caused by significant deficits in insulin-producing -cells. Insulin given exogenously does not exactly mimic its physiological secretion and carries the risk of developing hypoglycemia or secondary diabetic complications. Replenishment of deficient -cells through islet transplantation offers ideal therapeutic outcomes, yet the option is limited by the donor availability, graft survival and complications associated with the long-term use of immunosupressants (Bromberg et al, 2007; Gruessner and Gruessner, 2013). Exploiting the regenerative capacity of stem cells has emerged as a novel approach to complement the current therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
