Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high glucose conditions in-vitro and ameliorates drug induced diabetes in rats

Abstract

BackgroundDiabetes mellitus is affecting more than 300 million people worldwide. Current treatment strategies cannot prevent secondary complications. Stem cells due to their regenerative power have long been the attractive target for the cell-based therapies. Mesenchymal stem cells (MSCs) possess the ability to differentiate into several cell types and to escape immune recognition in vitro. MSCs can be differentiated into insulin-producing cells (IPCs) and could be an exciting therapy for diabetes but problems like poor engraftment and survivability need to be confronted. It was hypothesized that stromal cell derived factor- 1alpha (SDF-1alpha) will enhance therapeutic potential of stem cell derived IPCs by increasing their survival and proliferation rate.MethodsNovel culture conditions were developed to differentiate bone marrow derived mesenchymal stem cells (BMSCs) into IPCs by using endocrine differentiation inducers and growth factors via a three stage protocol. In order to enhance their therapeutic potential, we preconditioned IPCs with SDF-1alpha.ResultsOur results showed that SDF-1alpha increases survival and proliferation of IPCs and protects them from glucotoxicity under high glucose conditions in vitro. SDF-1alpha also enhances the glucose responsive insulin secretion in IPCs in vitro. SDF-1alpha preconditioning reverses hyperglycemia and increase serum insulin in drug induced diabetic rats.ConclusionsThe differentiation of BMSCs into IPCs and enhancement of their therapeutic potential by SDF-1alpha preconditioning may contribute to cell based therapies for diabetes.

MSCs ameliorates DPN induced cellular pathology via [Ca2+]i homeostasis and scavenging the pro‐inflammatory cytokines

“…The results clearly show reversal of the nerve conduction parameters. However the first step in this process is the control of hyperglycemia and it is well evidenced from animal studies of the current investigation as well as from our previous observation and published literature evidences (Jurewicz et al, ; Tariq, Masoud, Mehmood, Khan, & Riazuddin, ). We do not have affirmative piece of data on the long consistent control of hyperglycemia by i.v BM MSC transplantation, but our studies show a control of hyperglycemia and more significantly on the reversal or control of diabetic complications.…”

Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of “Neo-Islets,” Three-Dimensional Aggregates of Allogeneic Islet and “Mesenchymal Stem Cells”

“…A), 2x10e5 C57Bl/6 mouse islets ( N = 3), or vehicle ( N = 6) were administered i.p. to spontaneously diabetic NOD mice after blood glucose levels were normalized with slow‐release insulin pellets (Linbits) in order to reduce glucotoxic effects on the transplanted cells and to enhance their in vivo redifferentiation . By day 35–40 post‐Linbit treatment, Linbits are depleted, and hyperglycemia redeveloped in both islet‐ and vehicle‐treated NOD mice, as expected .…”

Differentiation of stem cells into insulin‐producing cells under the influence of nanostructural polyoxometalates

“…Three cell lines were used in this study. Human bone marrow adult mesenchymal stem cells (M-MSCs) were previously characterized for immunophenotype (Tomuleasa et al, 2009). Human umbilical vein endothelial cells*** (HUVECs) were a gift from Assoc.…”

“…The literature presents numerous in vitro differentiation strategies, using embryonic stem cells, induced pluripotent stem cells or adult MSCs, with or without genetic manipulation. The differentiation process can be imitated in vitro by adding proper growth factors and biomolecules (Tariq et al, 2013). Intestinal hormones, such as glucagon-like peptide 1 and its agonist exenatide (similar to exendin-4), gastrin, ghrelin, as well as growth factors, betacellulin (member of the EGF family), activin A (TGFβ family), fibroblast growth factor-7 or HGF have been reported to induce βcell proliferation and to improve their function (Desgraz et al, 2011).…”