CNS disease diminishes the therapeutic functionality of bone marrow mesenchymal stem cells.

CNS disease diminishes the therapeutic functionality of bone marrow mesenchymal stem cells. Exp Neurol. 2017 Jun 09;: Authors: Sargent A, Bai L, Shano G, Karl M, Garrison E, Ranasinghe L, Planchon SM, Cohen J, Miller RH Abstract Mesenchymal stem cells (MSCs) have emerged as a potentially powerful cellular therapy for autoimmune diseases including multiple sclerosis (MS). Based on their success in treating animal models of MS like experimental autoimmune encephalomyelitis (EAE), MSCs have moved rapidly into clinical trials for MS. The majority of these trials use autologous MSCs derived from MS patients, although it remains unclear how CNS disease may affect these cells. Here, we report that bone marrow MSCs derived from EAE mice lack therapeutic efficacy compared to naïve MSCs in their ability to ameliorate EAE. Treatment with conditioned medium from EAE-MSCs also fails to modulate EAE, and EAE-MSCs secrete higher levels of many pro-inflammatory cytokines compared to naïve MSCs. Similarly, MSCs derived from MS patients have less therapeutic efficacy than naïve MSCs in treating EAE and secrete higher levels of some of the same pro-inflammatory cytokines. Thus diseases like EAE and MS diminish the therapeutic functionality of bone marrow MSCs, prompting reevaluation about the ongoing use of autologous MSCs as a treatment for MS. PMID: 28602834 [PubMed - as supplied by publisher]
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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Purpose of review Autologous hematopoietic stem cell transplantation (HSCT) is a promising therapeutic modality for severe autoimmune diseases. In this review, we will outline the immunological mechanisms and the clinical evidence and experiences for therapeutic HSCT in autoimmune diseases, with particular focus on systemic sclerosis and multiple sclerosis. Recent findings Approximately 3000 patients with autoimmune diseases worldwide have been treated with HSCT. HSCT in systemic sclerosis has been shown in three randomized controlled trials to be associated with significant long-term event-free survival despite some ...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research
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Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Publication date: Available online 2 September 2019Source: Life SciencesAuthor(s): Sahar Rostami Mansoor, Ebrahim Zabihi, Maryam Ghasemi-KasmanAbstractMultiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). In attempt to identify an appropriate treatment for improving the neurological symptoms and remyelination process, autologous and allogenic transplantation of mesenchymal stem cells (MSCs) have been introduced as an effective therapeutic strategy in MS. MSCs are a heterogeneous subset of pluripotent non-hematopoietic stromal cells that are isolated from bone marrow, adip...
Source: Life Sciences - Category: Biology Source Type: research
Thyroid dysfunction (TD) frequently occurs as an autoimmune complication of immune reconstitution therapy (IRT), especially in individuals with multiple sclerosis treated with alemtuzumab, a pan-lymphocyte depleting drug with subsequent recovery of immune cell numbers. Less frequently, TD is triggered by highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV), or patients undergoing bone-marrow/hematopoietic-stem-cell transplantation (BMT/HSCT). In both alemtuzumab-induced TD and HIV/HAART patients, the commonest disorder is Graves ’ disease (GD), followed by hypothyr...
Source: European Thyroid Journal - Category: Endocrinology Source Type: research
Several autoimmune diseases including multiple sclerosis (MS) cause increased transcription of endogenous retroviruses (HERVs) normally repressed by heterochromatin. In parallel, HERV-derived sequences were reported to drive gene expression. Here, we have examined a possible link between promoter and enhancer divergent transcription and the production of HERV transcripts. We find that HERV-derived sequences are in general counter-selected at regulatory regions, a counter-selection that is strongest in brain tissues while very moderate in stem cells. By exposing T cells to the pesticide dieldrin, we further found that a ser...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Molecular Biology of Disease Articles Source Type: research
In this study, the experimental autoimmune encephalomyelitis (EAE) model, which is the most commonly model to mimic MS, was successfully established in cynomolgus monkeys. To evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (UCMSCs) on MS, we intravenously transplanted UCMSCs into cynomolgus monkeys with EAE. Our results showed that UCMSC transplantation significantly ameliorated the clinical symptoms of MS. Magnetic resonance imaging and clinical signs indicated that demyelination was obviously decreased after UCMSCs therapy. Moreover, the present study showed that the mechanisms, involved in...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Neurology - Category: Neurology Source Type: research
Joanna Mikulak1,2, Elena Bruni1,2, Ferdinando Oriolo1,2, Clara Di Vito1 and Domenico Mavilio1,2* 1Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy 2Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy The liver is considered a preferential tissue for NK cells residency. In humans, almost 50% of all intrahepatic lymphocytes are NK cells that are strongly imprinted in a liver-specific manner and show a broad spectrum of cellular heterogeneity. Hepatic NK (he-NK) cells play key roles in tuning liver immune response in b...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Physiology - Category: Physiology Source Type: research
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