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.
Highlights
Diabetes mellitus is affecting more than 300 million people worldwide
Treatment of bone marrow derived mesenchymal stem cells (BMSCs) with insulin-promoting factors such as nicotinamide, high glucose induction and growth factors such as activin A and glucagon-like peptide–1 (GLP-1) differentiate them into insulin producing cells (IPCs)
Our results demonstrated that Stromal cell derived factor-1alpha (SDF-1α) preconditioning of IPCs significantly enhanced cell viability as compared to control BMSCs and non-preconditioned IPCs under low as well as high glucose concentrations (Figure 3a) and showed better proliferation under different glucose concentrations (Figure 3c)
Summary
Diabetes mellitus is affecting more than 300 million people worldwide. 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. At least 285 million people were affected from diabetes in 2010 worldwide and this number is increasing day by day [2]. The treatment of the absolute insulin deficiency resulting from Type 1 diabetes is very. MSCs can be differentiated into insulin producing cells (IPCs) and their possible therapeutic potential for diabetes depends upon this differential ability [7,8,9]. The remedial use of MSCs is limited at present due to several problems such as poor engraftment, limited differentiation in host tissue [13] and differentiation of MSCs into unwanted lineages [14] by a variety of factors [15]
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