β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells

Abstract

Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into β-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous β-cells. Here we examined these questions by testing the ability of hBMSCs genetically modified to transiently express vascular endothelial growth factor (VEGF) or pancreatic-duodenal homeobox 1 (PDX1) to reverse diabetes and whether these cells were differentiated into β-cells or mediated recovery through alternative mechanisms. Human BMSCs expressing VEGF and PDX1 reversed hyperglycemia in more than half of the diabetic mice and induced overall improved survival and weight maintenance in all mice. Recovery was sustained only in the mice treated with hBMSCs-VEGF. However, de novo β-cell differentiation from human cells was observed in mice in both cases, treated with either hBMSCs-VEGF or hBMSCs- PDX1, confirmed by detectable level of serum human insulin. Sustained reversion of diabetes mediated by hBMSCs-VEGF was secondary to endogenous β-cell regeneration and correlated with activation of the insulin/IGF receptor signaling pathway involved in maintaining β-cell mass and function. Our study demonstrated the possible benefit of hBMSCs for the treatment of insulin-dependent diabetes and gives new insight into the mechanism of β-cell recovery after injury mediated by hBMSC therapy.

The Antidiabetic Effect of Mesenchymal Stem Cells vs. Nigella sativa Oil on Streptozotocin Induced Type 1 Diabetic Rats

“…Additionally; the anti-insulin immunostaining of the cells, used in this study, confirmed that the damage was mainly in the β-cells. This finding was shown in other studies after 25 days of diabetes induction [27] and after 6 weeks survival [28].…”

“…[5] Similar results were reported by Milanesi et al [28] who studied the transplantation of human bone marrow MSCs into diabetic animal models on histological and immunohistochemical basis. They found that the human stem cells had homed in the pancreas and regenerated into β-cells with complete cure after 6 weeks from transplantation [28].…”

Effect of pulsed electromagnetic field therapy on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells

“…They are also a class of stem cells with the potential for directional or multi-directional differentiation, and can differentiate into bone cells, cartilage cells, or fat cells. These cells can differentiate into osteogenic tissue, adipose tissue, and many other tissues under the influence of different factors (Shi et al, 2011;Milanesi et al, 2012). We speculate that PEMFs can help promote the directional differentiation of BMSCs into osteogenic tissue and inhibit the differentiation of BMSCs into other tissues, thereby promoting the healing of fractures.…”

Effect of Bone Marrow Versus Adipose Tissue Derived Mesenchymal Stem Cells on the Pancreas of Streptozotocin-Induced Diabetes Mellitus Type I in Adult Male Rats (Histological Study)

“…This supposition could occur through change in the tissue microenvironment which was considered the most important mechanism of action of the mesenchymal stem cells [37] . This change could explain the ability of human BMSCs to treat the autoimmune type of diabetes (type I) [38] most probably through the ability of BMSCs to stop anti β -cells specific T-cell proliferation in the pancreas. Furthermore they could protect the newly formed β -cells from being destroyed by T-cells through secretion of immunomodulatory factors [34] .…”