Multipotent mesenchymal stromal cells from patients with newly diagnosed type 1 diabetes mellitus exhibit preserved in vitro and in vivo immunomodulatory properties

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.

Genetic Modification of Stem Cells in Diabetes and Obesity

“…When transplanted into a streptozotocin (STZ)-induced diabetic mouse model, bone marrowderived MSCs were able to improve β-cell mass and increased insulin production, which resulted in a reversal of hyperglycemia [38][39][40][41]. Additionally, similar results were found when bone marrow-derived MSCs were obtained from donors with newly (6 weeks) diagnosed type I diabetes [41].…”

“…Additionally, similar results were found when bone marrow-derived MSCs were obtained from donors with newly (6 weeks) diagnosed type I diabetes [41].…”

Strength, corrosion resistance, and biocompatibility of ultrafine-grained Mg alloys after different modes of severe plastic deformation

“…Mesenchymal stromal/stem cells (MSCs) were isolated according to the standard techniques for the isolation of mononuclear cells from bone marrow of CBA mouse femurs using density gradient centrifugation [11]. The cells were cultured in Dulbecco's modified Eagle's medium (DMEM, high glucose) (Gibco), supplemented with 10% fetal bovine serum (FBS) in a humidified incubator at 95% relative humidity and 5% CO 2 at 37°C.…”

Adipose stem cells from chronic pancreatitis patients improve mouse and human islet survival and function

“…For example, MSCs from patients with rheumatoid arthritis [ 33 ], immune thrombocytopenic purpura [ 34 ], and multiple sclerosis [ 35 ] showed defects in critical cell functions and capability in tissue repair. In contrast, MSCs from systemic sclerosis and patients with type 1 diabetes seem to retain their immunosuppressive and tissue protective capabilities [ 33 , 36 ]. We have compared the cell phenotype, colony formation ability, multilineage differentiation ability, secretory characters, and immunosuppressive functions between MSCs harvested from healthy donors and CP patients.…”