Islet-like clusters derived from skeletal muscle-derived stem/progenitor cells for autologous transplantation to control type 1 diabetes in mice

Artif Cells Nanomed Biotechnol. 2018;46(sup3):S328-S335. doi: 10.1080/21691401.2018.1492421. Epub 2018 Jul 23.

Abstract

A population of muscle-derived stem/progenitor cells (MDSPCs) contained in skeletal muscle is responsible for muscle regeneration. MDSPCs from mouse muscle have been shown to be capable of differentiating into pancreatic islet-like cells. However, the potency of MDSPCs to differentiate into functional islet-like cluster remains to be confirmed. The therapeutic potential of autologous MDSPCs transplantation on type 1 diabetes still remains unclear. Here, we investigated a four-stage method to induce the differentiation of MDSPCs into insulin-producing clusters in vitro, and tested the autologous transplantation to control type 1 diabetes in mice. MDSPCs isolated from the skeletal muscles of mice possessed the ability to form islet-like clusters through several stages of differentiation. The expressions of pancreatic progenitor-related genes, insulin, and islet-related genes were significantly upregulated in islet-like clusters determined by the quantitative reverse transcription polymerase chain reaction. The autologous islet-like clusters transplantation effectively improved hyperglycaemia and glucose intolerance and increased the survival rate in streptozotocin-induced diabetic mice without the use of immunosuppressants. Taken together, these results provide evidence that MDSPCs from murine muscle tissues are capable of differentiating into insulin-producing clusters, which possess insulin-producing ability in vitro and in vivo, and have the potential for autologous transplantation to control type 1 diabetes.

Keywords: Diabetes mellitus; autologous transplantation; differentiation; islet-like clusters; muscle-derived stem cells.

MeSH terms

  • Animals
  • Autografts
  • Cell Differentiation*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy*
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Islets of Langerhans Transplantation*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myoblasts, Skeletal* / metabolism
  • Myoblasts, Skeletal* / pathology
  • Myoblasts, Skeletal* / transplantation