Abstract
BackgroundBone marrow multipotent mesenchymal stromal cells (MSCs) are a diverse subset of precursors that contribute to the homeostasis of the hematopoietic niche. MSCs can be isolated and expanded in vitro and have unique immunomodulatory and regenerative properties that make them attractive for the treatment of autoimmune diseases, including type 1 diabetes (T1D). Whether autologous or allogeneic MSCs are more suitable for therapeutic purposes has not yet been established. While autologous MSCs may present abnormal function, allogeneic cells may be recognized and rejected by the host immune system. Thus, studies that investigate biological characteristics of MSCs isolated from T1D patients are essential to guide future clinical applications.MethodsBone marrow-derived MSCs from recently diagnosed type 1 diabetes patients (T1D-MSCs) were compared with those from healthy individuals (C-MSCs) for morphological and immunophenotypic characteristics and for differentiation potential. Bioinformatics approaches allowed us to match absolute and differential gene expression of several adhesion molecules, immune mediators, growth factors, and their receptors involved with hematopoietic support and immunomodulatory properties of MSCs. Finally, the differentially expressed genes were collated for functional pathway enrichment analysis.ResultsT1D-MSCs and C-MSCs were similar for morphology, immunophenotype, and differentiation potential. Our absolute gene expression results supported previous literature reports, while also detecting new potential molecules related to bone marrow-derived MSC functions. T1D-MSCs showed intrinsic abnormalities in mRNA expression, including the immunomodulatory molecules VCAM-1, CXCL12, HGF, and CCL2. Pathway analyses revealed activation of sympathetic nervous system and JAK STAT signaling in T1D-MSCs.ConclusionsCollectively, our results indicate that MSCs isolated from T1D patients present intrinsic transcriptional alterations that may affect their therapeutic potential. However, the implications of these abnormalities in T1D development as well as in the therapeutic efficacy of autologous MSCs require further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0351-y) contains supplementary material, which is available to authorized users.
Highlights
Bone marrow multipotent mesenchymal stromal cells (MSCs) are a diverse subset of precursors that contribute to the homeostasis of the hematopoietic niche
Collectively, our results indicate that MSCs isolated from type 1 diabetes (T1D) patients present intrinsic transcriptional alterations that may affect their therapeutic potential
Murine bone marrow MSCs are physically close to most hematopoietic stem cells (HSCs) and express high levels of genes related to HSC maintenance and retention, which makes them important contributors for maturation of the hematopoietic compartment [6,7,8,9]
Summary
Bone marrow multipotent mesenchymal stromal cells (MSCs) are a diverse subset of precursors that contribute to the homeostasis of the hematopoietic niche. MSCs can be isolated and expanded in vitro and have unique immunomodulatory and regenerative properties that make them attractive for the treatment of autoimmune diseases, including type 1 diabetes (T1D). Multipotent mesenchymal stromal cells (MSCs) are a diverse subset of precursors found in the stromal fraction of the bone marrow and other adult tissues, presenting osteogenic, adipogenic, and chondrogenic differentiating potentials [1,2,3]. MSCs can be expanded in vitro and have unique immunomodulatory and regenerative properties, which render them attractive for treatment of autoimmune and inflammatory disorders [10]. The therapeutic effects of MSCs are partially due to their ability to produce and secrete a vast array of soluble mediators and other molecules with immunomodulatory properties, such as hepatocyte growth factor (HGF), indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2 (COX2), IL-10, prostaglandin E2, nitric oxide, and transforming growth factor beta 1 (TGFβ-1) [14]
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