Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment.
BACKGROUND
Stem cell differentiation is controlled by extracellular cues from the environment and by intrinsic genetic programs within the stem cell. The present study aimed to explore whether mesenchymal stromal cells (MSC) could improve hyperglycemia and insulin production in the diabetic microenvironment.


METHODS
We transplanted male porcine bone marrow-derived EGFP-expressing MSC directly into female diabetic porcine pancreas by multi-point injection. Enzyme-linked immunosorbent assay (ELISA) and fluorescent immunohistochemistry were used to analyze recipients' sera and pancreas tissues for assessment of the therapeutic effect.


RESULTS
Blood glucose levels decreased gradually in MSC-treated recipients from 15 days after the transplantation compared with untreated diabetic controls (15.94+/-0.31 mmol/L versus 16.66+/-0.11 mmol/L; P=0.01). Blood insulin increased and glucagons decreased notably in recipients from 2 weeks post-transplantation compared with untreated diabetic controls (0.049+/-0.004 microg/L versus 0.037+/-0.02 microg/L and 392.9+/-20.3 ng/L versus 433.1+/-27.6 ng/L). Hematoxylin and eosin (HE)-stained sections demonstrated that the number of islets from each section was markedly increased in recipients compared with that of diabetic controls (10.9+/-2.2 versus 4.6+/-1.4; P<0.05) and similar to that of normal controls (10.9+/-2.2 versus 12.6+/-2.6; P>0.05). The newly formed islets were smaller than normal islets (47.2+/-19.6 microm versus 119.6+/-27.7 microm; P<0.05). Analysis of pancreatic sections for EGFP in recipients indicated that the transplanted MSC survived within the pancreas. Insulin immunoreactivity of pancreatic islets showed that the newly formed islets expressed insulin.


CONCLUSIONS
MSC could improve diabetes upon pancreatic microenvironment without obvious immune rejections. This has theoretical and clinical applications.
Chang
C
C
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Niu
D
D
Zhou
H
H
Zhang
Y
Y
Li
F
F
Gong
F
F
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006943:Hyperglycemia / Q000628:therapy*; D016130:Immunophenotyping; D007328:Insulin / Q000172:deficiency* / Q000276:immunology; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000378:metabolism* / Q000601:surgery; D020127:Recovery of Function; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection
D001786:Blood Glucose; D007328:Insulin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins