Abstract
BackgroundType 1 diabetes mellitus (T1D) is characterized by autoimmune responses resulting in destruction of insulin-producing pancreatic beta cells. Multipotent mesenchymal stromal cells (MSCs) exhibit immunomodulatory potential, migratory capacity to injured areas and may contribute to tissue regeneration by the secretion of bioactive factors. Therefore, MSCs are considered as a promising approach to treat patients with different autoimmune diseases (AID), including T1D patients. Phenotypical and functional alterations have been reported in MSCs derived from patients with different AID. However, little is known about the properties of MSCs derived from patients with T1D. Since autoimmunity and the diabetic microenvironment may affect the biology of MSCs, it becomes important to investigate whether these cells are suitable for autologous transplantation. Thus, the aim of the present study was to evaluate the in vitro properties and the in vivo therapeutic efficacy of MSCs isolated from bone marrow of newly diagnosed T1D patients (T1D-MSCs) and to compare them with MSCs from healthy individuals (C-MSCs).MethodsT1D-MSCs and C-MSCs were isolated and cultured until third passage. Then, morphology, cell diameter, expression of surface markers, differentiation potential, global microarray analyses and immunosuppressive capacity were in vitro analyzed. T1D-MSCs and C-MSCs therapeutic potential were evaluated using a murine experimental model of streptozotocin (STZ)-induced diabetes.ResultsT1D-MSCs and C-MSCs presented similar morphology, immunophenotype, differentiation potential, gene expression of immunomodulatory molecules and in vitro immunosuppressive capacity. When administered into diabetic mice, both T1D-MSCs and C-MSCs were able to reverse hyperglycemia, improve beta cell function and modulate pancreatic cytokine levels.ConclusionsThus, bone marrow MSCs isolated from T1D patients recently after diagnosis are not phenotypically or functionally impaired by harmful inflammatory and metabolic diabetic conditions. Our results provide support for the use of autologous MSCs for treatment of newly diagnosed T1D patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0261-4) contains supplementary material, which is available to authorized users.
Highlights
Type 1 diabetes mellitus (T1D) is characterized by autoimmune responses resulting in destruction of insulin-producing pancreatic beta cells
Conclusions: bone marrow Multipotent mesenchymal stromal cell (MSC) isolated from T1D patients recently after diagnosis are not phenotypically or functionally impaired by harmful inflammatory and metabolic diabetic conditions
MSCs isolated from bone marrows of healthy donors (C-MSCs) and newly diagnosed T1D patients (T1DMSCs) appeared as typical monolayers of spindle-shaped fibroblast-like cells, with ability to adhere to plastic during in vitro expansion
Summary
Type 1 diabetes mellitus (T1D) is characterized by autoimmune responses resulting in destruction of insulin-producing pancreatic beta cells. Type 1 diabetes mellitus (T1D) is a chronic disease characterized by an autoimmune response in which cellular immunity plays a pivotal role in the selective destruction of insulin-producing pancreatic beta (β) cells, leading to metabolic dysfunction. While insulin replacement stands as the main therapeutic approach for T1D patients, it is insufficient to prevent long-term complications such as vascular dysfunction, retinopathy, and kidney failure [1]. Possible alternative treatments, such as human pancreas and islet transplantation, are limited by lack of sufficient donors, high costs, and need for chronic post-transplant immunosuppression [2]. These difficulties have prompted research into the development of alternative and innovative methods to treat T1D patients
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