Evaluation of stem cell differentiation in diabetic rats transplanted with bone marrow mesenchymal stem cells.
OBJECTIVE
Bone marrow mesenchymal stem cell (BM-MSC) transplantation has generated a great deal of excitement as a promising therapeutic strategy for diabetes mellitus. However, the exact mechanisms of reversing hyperglycemia remain elusive. Our objective was to investigate whether stem cell differentiation determined therapeutic efficacy.


METHODS
Wistar rats were rendered diabetic by an intraperitoneal injection of streptozotocin. BM-MSCs isolated from diabetic Wistar rats were analyzed for phenotype characteristics. Subsequently, BM-MSCs were transplanted into diabetic rats, followed by intravenous injection of recombinant lentiviruses encoding 2 different small hairpin RNAs (shRNAs) for specific interference with neurogenin 3 (Ngn3). We measured blood glucose levels and insulin and performed histological analysis of the pancreas.


RESULTS
BM-MSCs lowered blood glucose by increasing beta-cell mass compared with sham-operated controls, but this effect was inhibited by interference with the Ngn3 gene.


CONCLUSIONS
Differentiation of stem cells, including BM-MSCs and endogenous pancreatic stem cells, plays a major role in the process of reversing hyperglycemia.
Lin
P
P
Department of Endocrinology, Qilu Hospital, Shandong University, Shandong, China.
Chen
L
L
Yang
N
N
Sun
Y
Y
Xu
Y X
YX
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005786:Gene Expression Regulation; D006943:Hyperglycemia / Q000517:prevention & control; D050417:Insulin-Secreting Cells / Q000166:cytology; D016086:Lentivirus / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D016337:RNA, Catalytic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; C498696:Neurog3 protein, rat; C418481:hairpin ribozyme