Mesenchymal stem cells adopt beta-cell fate upon diabetic pancreatic microenvironment.
OBJECTIVE
: This study observed whether mesenchymal stem cells (MSCs) adopt beta-cell fate upon diabetic microenvironment.


METHODS
: 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.


RESULTS
: 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.


CONCLUSIONS
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.
Chang
Caihong
C
Department of Immunology Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wang
Xinjun
X
Niu
Deliang
D
Zhang
Zhan
Z
Zhao
Hongyang
H
Gong
Feili
F
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D024282:Genes, sry; D006085:Graft Survival; D018398:Homeodomain Proteins / Q000235:genetics; D007328:Insulin / Q000097:blood / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D042282:Microdissection; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D015534:Trans-Activators / Q000235:genetics
D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein