A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats

Abstract

BackgroundMany studies suggested mesenchymal stem cells (MSCs) transplantation as a new approach to control hyperglycemia in type 1 diabetes mellitus through differentiation mechanism. In contrary others believed that therapeutic properties of MSCs is depends on paracrine mechanisms even if they were not engrafted. This study aimed to compare these two approaches in control of hyperglycemia in STZ-induced diabetic rats.MethodsAnimals were divided into five groups: normal; diabetic control; diabetic received MSCs; diabetic received supernatant of MSCs; diabetic received co-administration of MSCs with supernatant. Blood glucose, insulin levels and body weight of animals were monitored during experiment. Immunohistochemical and immunofluorescence analysis were performed to monitor functionality and migration of labeled-MSCs to pancreas.ResultsFirst administration of MSCs within the first 3 weeks could not reduce blood glucose, but second administration significantly reduced blood glucose after week four compared to diabetic controls. Daily injection of supernatant could not reduce blood glucose as efficient as MSCs. Interestingly; Co-administration of MSCs with supernatant significantly reduced blood glucose more than other treated groups. Insulin levels and body weight were significantly increased in MSCs + supernatant-treated animals compared to other groups. Immunohistological analysis showed an increase in number and size of islets per section respectively in supernatant, MSCs and MSCs + supernatant-treated groups.ConclusionPresent study exhibited that repeated-injection of MSCs reduced blood glucose and increased serum insulin levels in recipient rats. Injection of supernatant could not reverse hyperglycemia as efficient as MSCs. Interestingly; co-administration of MSCs with supernatant could reverse hyperglycemia more than either group alone.

The impact of mesenchymal stem cells on doxorubicin‐induced testicular toxicity and progeny outcome of male prepubertal rats

“…In the present study, the reduction in the body as well as the testis weights caused by Dox was recovered significantly after the administration of a single dose of MSCs (2 × 10 6 ). The current result is consistent with Aali et al () who interpreted the improvement in body weight of rats after administration of a single dose of 2.5 × 10 6 MSCs.…”

Recipient Glycemic Micro-environments Govern Therapeutic Effects of Mesenchymal Stem Cell Infusion on Osteopenia

“…Current understanding of the antidiabetic effects of infused MSCs is unrelated to their transdifferentiation potential but to their paracrine impacts, of which immunomodulation is the research focus 25, 28, 80, 81. However, current data are controversial in whether MSC infusion could exert systemic immunomodulatory effects 76, 78 or local beneficial effects on pancreas micro-environments 25, 73, 77, which need MSC to migrate to pancreatic lymph nodes 25, 77.…”

Immortalized mesenchymal stem cells producing conditioned medium in a large scale for therapeutic usage

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