Mesenchymal Stem Cells Adopt β-Cell Fate Upon Diabetic Pancreatic Microenvironment

Abstract

: This study observed whether mesenchymal stem cells (MSCs) adopt beta-cell fate upon diabetic microenvironment. : We transplanted male porcine MSCs to diabetic female pigs by directly injecting into pancreas. Recipients' sera and pancreatic tissue were analyzed to assess the therapeutic effect. Islets were collected from the sections using laser-capture microdissection. The RNAs from these specimens were extracted and analyzed for insulin and pancreas duodenum homeobox 1 messenger RNA (mRNA) expression. SRY gene was detected from the specimens. : Compared with untreated diabetic controls, blood glucose level decreased greatly in recipients from 18 days (15.44 +/- 0.31 mmol/L vs 16.66 +/- 0.11 mmol/L) and insulin increased from 14 days (0.048 +/- 0.006 U/L vs 0.030 +/- 0.004 U/L). Hematoxylin and eosin-stained sections demonstrated increased islets in recipients and few lymphocytes present. The newly formed islets were smaller than normal islets (47.2 mum +/- 19.6 vs 119.6 +/- 27.7 mum). Reverse transcription-polymerase chain reaction showed that microdissected cells expressed insulin and pancreas duodenum homeobox 1 mRNA (79.3% +/- 16.2% of control, 65.2% +/- 14.8% of control, respectively). Immunoreactivity showed that the transplanted MSCs expressed insulin. SRY gene and insulin mRNA double-positive cells were found in microdissected cells by fluorescence in situ hybridization. This study shows that MSCs could adopt beta-cell fate in diabetic pancreatic microenvironment without obvious immune rejections. Stem cell transplantation in orthotope is a promising therapy for diabetes.