Transcriptional profiling reveals intrinsic mRNA alterations in multipotent mesenchymal stromal cells isolated from bone marrow of newly-diagnosed type 1 diabetes patients

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.

New Approaches to Dermatological Conditions Employing Mesenchymal Stem Cell Therapies

“…Recently, human MSCs derived from different tissues affected by AD showed immunomodulatory profile differences compared with healthy subjects, evidencing that MSCs could be involved in the AD pathogenesis [46] as it has been described in other immune-mediated diseases [47][48][49]. This would support the idea of an allogeneic MSCs therapy in AD [42].…”

Characterization of Mesenchymal Stem Cells Derived from Patients with Cerebellar Ataxia: Downregulation of the Anti-Inflammatory Secretome Profile

“…In accordance with previous studies [37,38], our findings suggest a limitation of autologous MSC therapy for CA. Recently, the bone marrow microenvironment and cellular functions were reported to be affected by disease states [39][40][41]. Thus, MSCs from patients with chronic diseases may have reprogrammed gene expression profiles.…”

“…For example, fibroblast growth factor-10 was markedly suppressed in the subjects with progressive idiopathic pulmonary fibrosis, and both TGF-β1 and SHH signaling were identified as critical mediators of this effect in MSCs [39]. MSCs from type 1 diabetes patients presented sympathetic nervous system signaling hyperactivity with an increase of β3-adrenergic receptor gene expression and upregulation of related pathway [40]. Moreover, metabolic syndrome seems to limit therapeutic potential of MSCs.…”

Suporte à acessibilidade, reprodutibilidade e transparência em uma plataforma integrada de análise de dados de expressão gênica

“…Finalmente, de modo a validar o funcionamento da plataforma, foi reproduzido parte de um estudo de análise de expressão gênica (LIMA et al, 2016) com o intuito de demonstrar as principais funcionalidades implementadas na plataforma para permitir a colaboração científica. Estudos adicionais também foram realizados para testar a plataforma SemanticSCo Web com base nos experimentos realizados na versão original da plataforma (GUARDIA, 2016).…”

“…De modo a validar o funcionamento da plataforma SemanticSco Web, um estudo de análise de expressão gênica foi realizado com o intuito de demonstrar as principais funcionalidades implementadas na plataforma para permitir a colaboração científica. Este estudo envolveu a reprodução de parte dos resultados obtidos em um trabalho envolvendo a análise comparativa de dados de Microarray Agilent One-color de pacientes com diabetes tipo I e indivíduos saudáveis (controle)(LIMA et al, 2016). Estes dados estão publicamente armazenados no repositório ArrayExpress sob o identificador E-MTAB-2976.O capítulo está estruturado da seguinte forma: a seção 5.1 apresenta uma visão geral do estudo utilizado para demonstrar o uso das novas funcionalidades da plataforma; a seção 5.2 apresenta os workflows construídos na plataforma para realização do estudo; a seção 5.3 apresenta os resultados obtidos com o estudo; e por fim, a seção 5.4 apresenta algumas conclusões.5.1 Visão geralO desenvolvimento deste estudo de caso foi dividido em três etapas.…”