الفهرس 
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Abstract
The present study was undertaken to evaluate the differentiation capacity and the efficiency of the therapeutic potential of human UCBMSCs in STZ-induced diabetic albino rats.
Human UCBMSCs were isolated, characterized and induced to differentiate into islet-like cell clusters using a combination of high-glucose, fetal bovine serum (FBS), pencillin and exendin-4. The differentiation capacity of UCBMSCs was assessed by insulin expression analysis using RT-PCR and intracellular insulin expression analysis using flow cytometry.
Seventy-five adult albino rats were used in this study. The animals were divided into 3 groups (twenty five animals each): the control group (Group I) fed with standard rat diet, STZ-induced diabetic group without stem cells transplantation (Group II) and STZ-induced diabetic group with stem cells transplantation (where differentiated UCBMSCs were injected inside the liver) (Group III): Ten weeks after the transplantation, the rats were sacrificed and the liver was carefully dissected out, sliced into small pieces, kept in formol-saline for 1week, and prepared for paraffin sections. The sections were subjected to the following stains: hematoxylin and eosin stain, Prussian blue stain to detect the impregnated cells in the liver and anti-human insulin immunostain to detect functioning human cells.
The islets like cell clusters in the cultures appeared about 7 days after MSCs differentiation; expressed cytoplasmic insulin cells, positive insulin expression using RT-PCR and could synthesize and secrete insulin at the (21 days). Flowcytometric analysis of insulin positive cells, showed that (1.1%) of undifferentiated cells was positive compared to 40% of differentiated cells. The mean content of total cellular insulin in undifferentiated cells was (0.75 ng/mg protein) while that of the differentiated cells was (14.28 ng/mg protein).
In rats of group I and group II, the sections stained with hematoxylin and eosin stain, showed normal liver architecture. In sections stained with Prussian blue stain, no blue cell clusters. In sections stained with anti-human insulin immunostain, negative cells inside liver parenchyma. In group III (STZ-diabetic group with stem cells transplantation), the sections stained with hematoxylin and eosin stain, showed intact cell clusters inside liver and around central veins. These cell clusters showed blue cytoplasm by Prussian blue stain indicating the presence of injected differentiated UCBMSCs. In sections stained with anti-human insulin immunostain, positive cell clusters were seen around central vein and inside liver parenchyma indicating that these cells functioning and secret insulin.
The present study showed that, human UCBMSCs are capable of differentiating into insulin-secreting cells (IPCs) in vitro by using high glucose media and exendin-4. These IPCs were transplanted into the liver of STZ-induced diabetic albino rats, they were being able to secrete insulin and partially control the diabetic status of the rats. Obviously, more research is needed to make possible the use of human UCBMSCs in diabetes therapeutic approaches and to determine its life span, dose and oncogencity.