Effect of mesenchymal stem cells transplantation on glycaemic profile & their localization in streptozotocin induced diabetic Wistar rats.
OBJECTIVE
Bone marrow is a rich source of adult stem cells that can differentiate into various cell types. Administration of mesenchymal stem cells (MSCs) in irradiated diabetic rat model has transiently shown to decrease blood glucose level. This study examines the effect of high dose and multiple injections of MSCs on glycemic profile, their localization and regeneration of islet in diabetic Wistar rat.


METHODS
The study was carried out in male Wistar rats categorized into three groups (n=6, in each group): Group 1 as control, group 2 streptozotocin (STZ) (50 mg/kg) induced diabetic group and group 3 experimental group; 5-bromo-2-deoxyuridine (BrdU) labelled allogenic MSCs were injected in the non-irradiated diabetic rat of the experimental group through tail vein. The blood glucose profile was subsequently monitored at regular intervals. Rats were sacrificed on day 45 and pancreas was examined for localization of BrdU labelled stem cells by immunofluorescence and islet-neogenesis by immunohistochemistry .


RESULTS
There was a significant reduction in blood glucose level after administration of MSCs in the experimental group (P<0.001). The presence of BrdU labelled MSCs in islet suggested their localization in the pancreas. Co-expression of anti-BrdU and anti-insulin antibody indicated trans-differentiation / fusion into insulin producing cells evidenced by significant increase in total number of islet (P=0.004) and insulin positive cells ( P<0.0001) in experimental group.


CONCLUSIONS
Our results showed that the MSCs administration in non-irradiated diabetic Wistar rat reduced hyperglycaemia and was accompanied by increased islet-neogenesis, possibly through trans-differentiation/fusion.
Shobhit
S
Bhansali
Vinod
V
Kumar
Uma Nahar
UN
Saikia
Bikash
B
Medhi
Vivekanand
V
Jha
Anil
A
Bhansali
Department of Endocrinology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Pinaki
P
Dutta
D000818:Animals; D001786:Blood Glucose; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000628:therapy*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000628:therapy*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats
D001786:Blood Glucose; D007328:Insulin