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Mesenchymal stem cell scleroderma

Alexandra Maria Giovanna Brunasso, Cesare Massone
In systemic sclerosis (SSc), the development of fibrosis seems to be a consequence of the initial ischemic process related to an endothelial injury. The initial trigger event in SSc is still unknown, but circulating progenitor cells (CPCs) might play a key role. Such cells have the ability to traffic into injury sites, exhibiting inflammatory features of macrophages, tissue remodeling properties of fibroblasts, and vasculogenesis functions of endothelial cells. The different subsets of CPCs described thus far in SSc arise from a pool of circulating monocyte precursors (CD14 (+) cells) and probably correspond to a different degree of differentiation of a single cell of origin...
2016: F1000Research
Audrey Cras, Dominique Farge, Thierry Carmoi, Jean-Jacques Lataillade, Dan Dan Wang, Lingyun Sun
Current systemic therapies are rarely curative for patients with severe life-threatening forms of autoimmune diseases (ADs). During the past 15 years, autologous hematopoietic stem cell transplantation has been demonstrated to cure some patients with severe AD refractory to all other available therapies. As a consequence, ADs such as lupus and scleroderma have become an emerging indication for cell therapy. Multipotent mesenchymal stem cells (MSCs), isolated from bone marrow and other sites, display specific immunomodulation and anti-inflammatory properties and appear as ideal tools to treat such diseases...
2015: Arthritis Research & Therapy
Perrine Guillaume-Jugnot, Aurélie Daumas, Jérémy Magalon, Elisabeth Jouve, Pierre-Sébastien Nguyen, Romain Truillet, Stéphanie Mallet, Dominique Casanova, Laurent Giraudo, Julie Veran, Françoise Dignat-George, Florence Sabatier, Guy Magalon, Brigitte Granel
OBJECTIVE: Impaired hand function greatly contributes to disability and reduced quality of life in SSc patients. Autologous adipose-derived stromal vascular fraction (ADSVF) is recognized as an easily accessible source of regenerative cells. We reported positive 6-month safety and efficacy results from an open-label clinical trial assessing s.c. injection of autologous ADSVF into the fingers in SSc patients. The objective of this report is to describe the effects at 12 months. METHODS: Twelve females, mean age 54...
February 2016: Rheumatology
Fernando Vázquez-Villa, Marcos García-Ocaña, José A Galván, Jorge García-Martínez, Carmen García-Pravia, Primitiva Menéndez-Rodríguez, Carmen González-del Rey, Luis Barneo-Serra, Juan R de Los Toyos
The COL11A1 human gene codes for the α1 chain of procollagen 11A1 and mature collagen 11A1, an extracellular minor fibrillar collagen. Under regular conditions, this gene and its derived products are mainly expressed by chondrocytes and mesenchymal stem cells as well as osteoblasts. Normal epithelial cells and quiescent fibroblasts from diverse locations do not express them. Mesenchyme-derived tumors and related conditions, such as scleroderma and keloids, are positive for COL11A1/(pro)collagen 11A1 expression, as well as high-grade human gliomas/glioblastomas...
April 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Chider Chen, Kentaro Akiyama, Dandan Wang, Xingtian Xu, Bei Li, Alireza Moshaverinia, Frank Brombacher, Lingyun Sun, Songtao Shi
Fibrillin-1 (FBN1) deficiency-induced systemic sclerosis is attributed to elevation of interleukin-4 (IL4) and TGF-β, but the mechanism underlying FBN1 deficiency-associated osteopenia is not fully understood. We show that bone marrow mesenchymal stem cells (BMMSCs) from FBN1-deficient (Fbn1(+/-)) mice exhibit decreased osteogenic differentiation and increased adipogenic differentiation. Mechanistically, this lineage alteration is regulated by IL4/IL4Rα-mediated activation of mTOR signaling to down-regulate RUNX2 and up-regulate PPARγ2, respectively, via P70 ribosomal S6 protein kinase (P70S6K)...
January 12, 2015: Journal of Experimental Medicine
Nicolas Serratrice, Laurie Bruzzese, Jérémy Magalon, Julie Véran, Laurent Giraudo, Houssein Aboudou, Djaffar Ould-Ali, Pierre Sébastien Nguyen, Olivier Bausset, Aurélie Daumas, Dominique Casanova, Brigitte Granel, Lucile Andrac-Meyer, Florence Sabatier, Guy Magalon
INTRODUCTION: Scleroderma is characterized by cutaneous manifestations that mainly affect the hands, arms and face. As of today, there is no treatment for fibrotic skin lesions of scleroderma. Previously we generated and validated a model of scleroderma-like skin sclerosis in nude mice, appropriate to inject human derived products. We showed that the subcutaneous injection of micro-fat (MF), purified and injected using small caliber cannulas, have anti-fibrotic and pro-angiogenic effects and appears more suitable for the treatment of skin lesions of scleroderma compared to the gold standard (Coleman's technique or macro-fat)...
2014: Stem Cell Research & Therapy
Paola Cipriani, Paola Di Benedetto, Piero Ruscitti, Antonio Francesco Campese, Vasiliki Liakouli, Francesco Carubbi, Ilenia Pantano, Onorina Berardicurt, Isabella Screpanti, Roberto Giacomelli
INTRODUCTION: To assess if an impaired cross-talk between endothelial cells (ECs) and perivascular/multipotent mesenchymal stem cells (MSCs) might induce a perturbation of vascular repair and leading to a phenotypic switch of MSC toward myofibroblast in Systemic Sclerosis (SSc). METHODS: We investigated different angiogenic and profibrotic molecules in a tridimentional matrigel assay, performing co-cultures with endothelial cells (ECs) and bone marrow derived MSCs from patients and healthy controls (HC)...
2014: Arthritis Research & Therapy
Brigitte Granel, Aurélie Daumas, Elisabeth Jouve, Jean-Robert Harlé, Pierre-Sébastien Nguyen, Christian Chabannon, Nathalie Colavolpe, Jean-Charles Reynier, Romain Truillet, Stéphanie Mallet, Antoine Baiada, Dominique Casanova, Laurent Giraudo, Laurent Arnaud, Julie Veran, Florence Sabatier, Guy Magalon
BACKGROUND: In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability...
December 2015: Annals of the Rheumatic Diseases
Isabel Sánchez-Berná, Carlos Santiago-Díaz, Juan Jiménez-Alonso
Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases...
January 20, 2015: Medicina Clínica
Chider Chen, Kentaro Akiyama, Takayoshi Yamaza, Yong-Ouk You, Xingtian Xu, Bei Li, Yimin Zhao, Songtao Shi
Bone marrow mesenchymal stem cells (BMMSCs) are capable of differentiating into multiple cell types and regulating immune cell response. However, the mechanisms that govern the immunomodulatory properties of BMMSCs are still not fully elucidated. Here we show that telomerase-deficient BMMSCs lose their capacity to inhibit T cells and ameliorate the disease phenotype in systemic sclerosis mice. Restoration of telomerase activity by telomerase reverse transcriptase (TERT) transfection in TERT(-/-) BMMSCs rescues their immunomodulatory functions...
March 2014: EMBO Molecular Medicine
A Daumas, J Eraud, A Hautier, F Sabatier, G Magalon, B Granel
Systemic sclerosis is a disorder involving the connective tissue, arterioles and microvessels. It is characterized by skin and visceral fibrosis and ischemic phenomena. Currently, therapy is limited and no antifibrotic treatment has proven its efficacy. Beyond some severe organ lesions (pulmonary arterial hypertension, pulmonary fibrosis, scleroderma renal crisis), which only concern a minority of patients, the skin sclerosis of hands and face and the vasculopathy lead to physical and psychological disability in most patients...
December 2013: La Revue de Médecine Interne
P Cipriani, P Di Benedetto, V Liakouli, B Del Papa, M Di Padova, M Di Ianni, A Marrelli, E Alesse, R Giacomelli
Systemic sclerosis (SSc) is a chronic disease, with early activation of the immune system. The aim of our work was to address how SSc-mesenchymal stem cells (MSCs), although senescent, might preserve specific immunomodulatory abilities during SSc. MSCs were obtained from 10 SSc patients and 10 healthy controls (HC). Senescence was evaluated by assessing cell cycle, β-galactosidase (β-Gal) activity, p21 and p53 expression; doxorubicin was used as acute senescence stimulus to evaluate their ability to react in stressed conditions...
August 2013: Clinical and Experimental Immunology
H-M Lorenz
No abstract text is available yet for this article.
April 2013: Deutsche Medizinische Wochenschrift
M Orciani, S Svegliati, S Gorbi, T Spadoni, R Lazzarini, F Regoli, R Di Primio, A Gabrielli
Scleroderma is a chronic systemic autoimmune disease (primarily of the skin) characterized by fibrosis (or hardening), vascular alterations and autoantibodies production.There are currently no effective therapies against this devastating and often lethal disorder. Despite the interest for the immunomodulatory effects of mesenchymal stem cells (MSCs) in autoimmune diseases, the role of MSCs in scleroderma is still unknown. A pivotal role in scleroderma onset is played by oxidative stress associated with the accumulation of great amounts of reactive oxygen species (ROS)...
January 2013: Journal of Biological Regulators and Homeostatic Agents
Paola Cipriani, Alessandra Marrelli, Paola Di Benedetto, Vasiliki Liakouli, Francesco Carubbi, Piero Ruscitti, Saverio Alvaro, Ilenia Pantano, Antonio Francesco Campese, Paola Grazioli, Isabella Screpanti, Roberto Giacomelli
INTRODUCTION: Vascular involvement is a key feature of Systemic sclerosis (SSc). Although the pericytes/endothelial cells (ECs) cross-talk regulates vessels formation, no evidences about the pericytes contribution to ineffective angiogenesis in SSc are available. Recent findings showed similarities between pericytes and Bone Marrow Mesenchymal Stem Cells (BM-MSCs). Due to difficulties in pericytes isolation, this work explores the possibility to use BM-MSCs as pericytes surrogate, clarifying their role in supporting neo-angiogenesis during SSc...
July 2013: Angiogenesis
Tomoaki Iwayama, Lorin E Olson
Fibrosis is the principal characteristic of the autoimmune disease known as scleroderma or systemic sclerosis (SSc). Studies published within the last three years suggest central involvement of platelet-derived growth factors (PDGFs) in SSc-associated fibrosis. PDGFs may also be involved in SSc-associated autoimmunity and vasculopathy. The PDGF signaling pathway is well understood and PDGF receptors are expressed on collagen-secreting fibroblasts and on mesenchymal stem and/or progenitor cells that may affect SSc in profound and unexpected ways...
February 2013: Current Rheumatology Reports
Jan Voswinkel, Sabine Francois, Jean-Marc Simon, Marc Benderitter, Norbert-Claude Gorin, Mohamad Mohty, Loïc Fouillard, Alain Chapel
Mesenchymal stem cells (MSC), multipotent adult stem cells, feature the potential to regenerate tissue damage and, in parallel, inhibit inflammation and fibrosis. MSC can be safely transplanted in autologous and allogeneic ways as they are non-immunogenic, and consequently represent a therapeutic option for refractory connective tissue diseases, fibrosing diseases like scleroderma and fistulizing colitis like in Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, and 22 are on autoimmune diseases...
October 2013: Clinical Reviews in Allergy & Immunology
Paola Cipriani, Francesco Carubbi, Vasiliki Liakouli, Alessandra Marrelli, Carlo Perricone, Roberto Perricone, Edoardo Alesse, Roberto Giacomelli
In this review we report the recent progresses, available in the literature, concerning the biology and the potential therapeutic role of both mesenchymal stem cells (MSCs) and hematopoietic stem cells in autoimmune diseases. Mesenchymal stem cells (MSCs) are responsible for the normal turnover and maintenance of adult mesenchymal tissues and their pleiotropic nature allows them to sense and respond to an event in the local environment, be it injury or inflammation. Recently, MSCs have been shown to have immune-modulatory properties and immunosuppressive capacities, acting on different immune cells both in vitro and in vivo, in addition to an immunologically privileged phenotype...
May 2013: Autoimmunity Reviews
Linda Badri, Vibha N Lama
Mesenchymal stem cells (MSCs) have been demonstrated to reside in human adult organs. However, mechanisms of migration of these endogenous MSCs within their tissue of origin are not well understood. Here, we investigate migration of human adult lung-resident (LR) mesenchymal progenitor cells. We demonstrate that bioactive lipid lysophosphatidic acid (LPA) plays a principal role in the migration of human LR-MSCs through a signaling pathway involving LPA1-induced β-catenin activation. LR-MSCs isolated from human lung allografts and lungs of patients with scleroderma demonstrated a robust migratory response to LPA in vitro...
September 2012: Stem Cells
Vetnizah Juniantito, Takeshi Izawa, Takahiro Yuasa, Chisa Ichikawa, Miyuu Tanaka, Mitsuru Kuwamura, Jyoji Yamate
Cellular characteristics of myofibroblasts and its possible origin with mesenchymal stem cell nature in scleroderma remain to be investigated. We analyzed these cells in scleroderma induced in F344 rats by bleomycin (BLM) by immunolabeling using a panel of marker antibodies for cytoskeletons (vimentin, desmin, α-smooth muscle actin (α-SMA)) and stromal stem cells (Thy-1, A3). Skin samples were collected at 1, 2, 3, and 4 weeks after initiation of subcutaneous injections of BLM (100 μl of 1 mg/ml, daily)...
July 2013: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
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