Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology

Growing knowledge on the biology of mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for rheumatologic disorders. Historically, their potential to differentiate into cells of the bone and cartilage lineages has led to a variety of experimental strategies to investigate whether MSCs can be used for tissue engineering approaches. Beyond this potential, MSCs also display immunosuppressive properties, which have prompted research on their capacity to suppress local inflammation and tissue damage in a variety of inflammatory autoimmune diseases and, in particular, in rheumatoid arthritis. Currently, an emerging field of research comes from the possibility that these cells, through their trophic/regenerative potential, may also influence the course of chronic degenerative disorders and prevent cartilage degradation in osteoarthritis. This review focuses on these advances, specifically on the biological properties of MSCs, including their immunoregulatory characteristics, differentiation capacity and trophic potential, as well as the relevance of MSC-based therapies for rheumatic diseases

Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications

Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that are isolated from many adult tissues, in particular from the bone marrow and adipose tissue. Along with their capacity for differentiating into cells of mesodermal lineage, such as adipocytes, osteoblasts and chondrocytes, these cells have also generated great interest for their ability to display immunomodulatory capacities. Indeed, a major breakthrough came with the finding that they are able to induce peripheral tolerance, suggesting they may be used as therapeutic tools in immune-mediated disorders. The present review aims at discussing the current knowledge on the targets and mechanisms of MSC-mediated immunosuppression as well as the potential use of MSCs as modulators of immune responses in a variety of diseases related to alloreactive immunity or autoimmunit

Mesenchymal Stem Cells in Systemic Sclerosis: Allogenic or Autologous Approaches for Therapeutic Use?

Systemic sclerosis (SSc) is a rare autoimmune disease, which is potentially lethal. The physiopathology of the disease is still incompletely elucidated although the role of fibroblasts, endothelial cells (ECs), immune cells. and the environment (i.e., oxidative stress) has been demonstrated. This is an intractable disease with an urgent need to provide better therapeutic options to patients. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach thanks to the number of trophic and pleiotropic properties they exert. Among these, MSCs display anti-fibrotic, angiogenic, and immunomodulatory capacities that might be of interest in the treatment of SSc by acting on different processes that are dysregulated in the disease. In the recent years, the therapeutic effectiveness of MSCs has been demonstrated in different preclinical animal models and is being investigated in phase I clinical trials. Both allogenic and autologous transplantation of MSCs isolated from bone marrow or adipose tissue is being evaluated. The rationale for using allogenic MSCs in SSc, as well as in other autoimmune diseases, is based on the possibility that autologous MSCs might be altered in these diseases. In SSc, reports from the literature are controversial. Nevertheless, the role of the oxidative environment and of the crosstalk with neighboring cells (fibroblasts and ECs) on the functional properties of MSCs has been reported. Here, we review the preclinical and clinical data reporting the interest of MSC-based treatment in SSc and question the use of autologous or allogeneic MSCs in perspective of clinical applications

Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes

Chondrogenesis is a process involving stem-cell differentiation through the coordinated effects of growth/differentiation factors and extracellular matrix (ECM) components. Recently, mesenchymal stem cells (MSCs) were found within the cartilage, which constitutes a specific niche composed of ECM proteins with unique features. Therefore, we hypothesized that the induction of MSC differentiation towards chondrocytes might be induced and/or influenced by molecules from the microenvironment. Using microarray analysis, we previously identified genes that are regulated during MSC differentiation towards chondrocytes. In this study, we wanted to precisely assess the differential expression of genes associated with the microenvironment using a large-scale real-time PCR assay, according to the simultaneous detection of up to 384 mRNAs in one sample. Chondrogenesis of bone-marrow-derived human MSCs was induced by culture in micropellet for various periods of time. Total RNA was extracted and submitted to quantitative RT-PCR. We identified molecules already known to be involved in attachment and cell migration, including syndecans, glypicans, gelsolin, decorin, fibronectin, and type II, IX and XI collagens. Importantly, we detected the expression of molecules that were not previously associated with MSCs or chondrocytes, namely metalloproteases (MMP-7 and MMP-28), molecules of the connective tissue growth factor (CTGF); cef10/cyr61 and nov (CCN) family (CCN3 and CCN4), chemokines and their receptors chemokine CXC motif ligand (CXCL1), Fms-related tyrosine kinase 3 ligand (FlT3L), chemokine CC motif receptor (CCR3 and CCR4), molecules with A Disintegrin And Metalloproteinase domain (ADAM8, ADAM9, ADAM19, ADAM23, A Disintegrin And Metalloproteinase with thrombospondin type 1 motif ADAMTS-4 and ADAMTS-5), cadherins (4 and 13) and integrins (α4, α7 and β5). Our data suggest that crosstalk between ECM components of the microenvironment and MSCs within the cartilage is responsible for the differentiation of MSCs into chondrocytes

Characterization of Degraded Cartilage Using Confocal Raman Microscopy

Osteoarthritis is a degenerative disease with pathological changes at the molecular level. Moreover, the damage to articular cartilage is irreversible. Early detection and the ability to follow the progression of osteoarthritis are essential to anticipate management. To characterize degraded human articular cartilage and to identify cellular changes that are precursors of phenotypic matrix changes in osteoarthritis, normal and degraded articular cartilage explants were harvested from the same patient’s knee after informed consent. The blocks were washed several times (four times) with phosphate-buffered saline (often abbreviated to PBS) and then fixed on CaF2 slides using Cell-Tak® (an adhesive glue), and the whole set was placed in different Petri dishes containing PBS for Raman measurements. The analysis of the spectroscopic data allowed to differentiate degraded cartilage from normal cartilage by applying intensity ratios of some Raman bands and/or spectral regions. In addition, peaks at 864, 929, 945, 1107, 1386, and 2887 cm−1 were identified as characteristic Raman markers of degraded cartilage. The use of confocal Raman microscopy (CRM) has proven to be relevant in providing biochemical information necessary to characterize OA cartilage. CRM appears to be a powerful tool for the diagnosis and therapeutic evaluation of osteoarthritis in both early and late stages

Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells

Previous studies have reported that mesenchymal stem cells (MSC) may be isolated from the synovial membrane by the same protocol as that used for synovial fibroblast cultivation, suggesting that MSC correspond to a subset of the adherent cell population, as MSC from the stromal compartment of the bone marrow (BM). The aims of the present study were, first, to better characterize the MSC derived from the synovial membrane and, second, to compare systematically, in parallel, the MSC-containing cell populations isolated from BM and those derived from the synovium, using quantitative assays. Fluorescent-activated cell sorting analysis revealed that both populations were negative for CD14, CD34 and CD45 expression and that both displayed equal levels of CD44, CD73, CD90 and CD105, a phenotype currently known to be characteristic of BM-MSC. Comparable with BM-MSC, such MSC-like cells isolated from the synovial membrane were shown for the first time to suppress the T-cell response in a mixed lymphocyte reaction, and to express the enzyme indoleamine 2,3-dioxygenase activity to the same extent as BM-MSC, which is a possible mediator of this suppressive activity. Using quantitative RT-PCR these data show that MSC-like cells from the synovium and BM may be induced to chondrogenic differentiation and, to a lesser extent, to osteogenic differentiation, but the osteogenic capacities of the synovium-derived MSC were significantly reduced based on the expression of the markers tested (collagen type II and aggrecan or alkaline phosphatase and osteocalcin, respectively). Transcription profiles, determined with the Atlas Human Cytokine/Receptor Array, revealed discrimination between the MSC-like cells from the synovial membrane and the BM-MSC by 46 of 268 genes. In particular, activin A was shown to be one major upregulated factor, highly secreted by BM-MSC. Whether this reflects a different cellular phenotype, a different amount of MSC in the synovium-derived population compared with BM-MSC adherent cell populations or the impact of a different microenvironment remains to be determined. In conclusion, although the BM-derived and synovium-derived MSC shared similar phenotypic and functional properties, both their differentiation capacities and transcriptional profiles permit one to discriminate the cell populations according to their tissue origin

Women's contribution to stem cell research for osteoarthritis: an opinion paper

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Revue d'histoire du Bas-Saint-Laurent, vol. 12 (3-4)

Mot de l'éditeur -- Au micro de CJBR -- La grande histoire de CJBR -- Jules-A. Brillant et le poste CJBR -- Avec CJBR, un bon en avant pour le Bas St-Laurent -- CJBR, l'école -- L'annonceur: un éducateur populaire -- Sandy Burgess : le journaliste que j'ai connu -- "Ce pays qui est le mien" -- Un demi-siècle d'information: que de nouvelles! -- Journaliste de père en fils à CJBR -- Le théâtre à CJBR -- 50 ans de musique à CJBR, le château fort de la mélodie française -- Poésie, théâtre, jazz et originalité avec Michel Garneau -- Les "Chroniques du dimanche", l'âge d'or de la critique culturelle à CJBR -- "Si CJBR m'était conté..." -- L'évolution technologique, un élément-clef de l'histoire des 50 ans de radiodiffusion -- La publicité à CJBR, quarante ans de croissance -- Des pionnières à CJBR -- 1958-1972, des années enrichissantes -- De Trois-Pistoles à Rimouski -- Le sport et son enracinement dans le milieu régional -- "Debout c'est l'heure", c'est Jean Brisson qui sonne le réveil -- "Par une belle journée de tempête" -- Et on repart vers la centain