Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high gluc
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RESEARCH
Open Access
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 Muhammad Tariq1,2*, Muhammad Sharif Masoud1,3, Azra Mehmood1, Shaheen N Khan1 and Sheikh Riazuddin1
Abstract Background: Diabetes 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. Methods: Novel 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. Results: Our 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. Conclusions: The differentiation of BMSCs into IPCs and enhancement of their therapeutic potential by SDF-1alpha preconditioning may contribute to cell based therapies for diabetes. Keywords: Diabetes mellitus, Mesenchymal stem cells, Differentiation, Preconditioning, SDF-1α
Background Diabetes mellitus (DM), a life threatening single-cell metabolic disorder, is defined by the presence of hyperglycemia due to damage or faulty pancreatic beta cells. Type 1 diabetes results from T-cell mediated autoimmune demolition of β-cells [1]. 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 * Correspondence: [email protected] 1 National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan 2 Current Affiliation: Department of Biotechnology, Mirpur University of Science and Technology, Mirpur, AK, Pakistan Full list of author information is available at the end of the article
challenging. Despite significant advances in the manufacture, modification and delivery of insulin, insulin therapy remains relatively risky and cannot prevent secondary complications. Islet-transplantation, the most successful treatment
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