Transplantation of insulin-producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice

Cell Transplant. 2011;20(3):455-66. doi: 10.3727/096368910X522270. Epub 2010 Aug 18.


Diabetes mellitus can be treated with islet transplantation, although there is a scarcity of donors. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord stroma could be induced to differentiate into insulin-producing cells and the effects of retro-orbital injection of human insulin-producing cells for the treatment of nonobese diabetic (NOD) mice. MSCs were isolated from human umbilical cord stroma and induced to differentiate into insulin-producing cells using differentiation medium. Differentiated cells were evaluated by immunocytochemistry, RT-PCR, and real-time PCR. C-peptide release, both spontaneous and after glucose challenge, was measured by ELISA. Insulin-producing cells were then transplanted into NOD mice. Blood glucose levels and body weights were monitored weekly. Human nuclei and C-peptide were detected in mouse livers by immunohistochemistry. Pancreatic β-cell development-related genes were expressed in the differentiated insulin-producing cells. Differentiated cells' C-peptide release in vitro increased after glucose challenge. Further, in vivo glucose tolerance tests showed that blood sugar levels decreased after the cells' transplantation into NOD mice. After transplantation, insulin-producing cells containing human C-peptide and human nuclei were located in the liver. Thus, we demonstrated that differentiated insulin-producing cells from human umbilical cord stromal MSCs transplanted into NOD mice could alleviate hyperglycemia in diabetic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • C-Peptide / analysis
  • Cell Differentiation
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / therapy*
  • Disease Models, Animal
  • Glucose / pharmacology
  • Humans
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin-Secreting Cells / transplantation*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred NOD
  • Stromal Cells / cytology
  • Umbilical Cord / cytology*


  • Blood Glucose
  • C-Peptide
  • Insulin
  • Glucose