Mesenchymal stem cell scleroderma

BACKGROUND: Inflammation and fibrosis of the skin are characteristics of localized scleroderma (LS). Emerging evidence has demonstrated that exosomes from human adipose tissue-derived mesenchymal stem cells (ADSC-Exo) could alleviate skin fibrosis. OBJECTIVE: The impact and potential mechanism of ADSC-Exo on LS fibrosis was examined. METHODS: ADSC-Exo was isolated and identified. The effects of ADSC-Exo on the abilities of proliferation and migration of LS-derived fibroblasts (LSFs) were assessed by CCK-8 and scratch assays, respectively...

Fibrosis is regulated by interactions between immune and mesenchymal cells. However, the capacity of cell types to modulate human fibrosis pathology is poorly understood due to lack of a fully humanized model system. MISTRG6 mice were engineered by homologous mouse/human gene replacement to develop an immune system like humans when engrafted with human hematopoietic stem cells (HSCs). We utilized MISTRG6 mice to model scleroderma by transplantation of healthy or scleroderma skin from a patient with pansclerotic morphea to humanized mice engrafted with unmatched allogeneic HSC...

Systemic sclerosis (SSc) refers to an autoimmune disease characterized by immune dysfunction, vascular endothelial damage, and multi-organ fibrosis. Thus far, this disease is incurable, and its high mortality rate is significantly correlated with fibrotic events. Fibrosis has been confirmed as a difficult clinical treatment area that should be urgently treated in clinical medicine. Mesenchymal stem cells (MSCs) exhibit immunomodulatory, pro-angiogenic, and anti-fibrotic functions. MSCs-derived extracellular vesicles (EVs) have aroused rising interest as a cellular component that retains the functions of MSCs while circumventing the possible adverse effects of MSCs...

Scleroderma is a rare, potentially fatal, clinically heterogeneous, systemic autoimmune connective tissue disorder that is characterised by progressive fibrosis of the skin and visceral organs, vasculopathy, and immune dysregulation. The more severe form of the disease, diffuse cutaneous scleroderma (dcSSc), has no cure and limited treatment options. Haematopoietic stem cell transplantation has emerged as a potentially disease-modifying treatment but faces challenges such as toxicity associated with fully myeloablative conditioning and recurrence of autoimmunity...

Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-β...

Contribution of mesenchymal stromal cell transplantation in systemic scleroderma Systemic scleroderma is a rare chronic autoimmune disease with the highest mortality rate among rheumatologic diseases. Its pathophysiology is based on three mechanisms: endothelial damage with initial vasculopathy, activation of the immune response, progressive fibrosis of the skin and various organs. Cellular therapy allows to envision new perspectives: autologous hematopoietic stem cell transplantation has been widely validated to treat severe forms of the disease, but its use is restricted to the most severely affected patients and contraindicated in advanced forms of the disease...

Localized scleroderma (LoS) is a rare chronic disease with extensive tissue fibrosis, inflammatory infiltration, microvascular alterations, and epidermal appendage lesions. However, a deeper understanding of the pathogenesis and treatment strategies of LoS is currently limited. In the present work, a proteome map of LoS skin is established, and the pathological features of LoS skin are characterized. Most importantly, a human-induced pluripotent stem cell-derived epithelial and mesenchymal (EM) organoids model in a 3D culture system for LoS therapy is established...

Although a number of new immunosuppressive agents and biologics have been approved for treating various autoimmune inflammatory rheumatic diseases, there remains a substantial number of patients who have no clinical response or limited clinical response to these available treatments. Use of cellular therapies is a novel approach for the treatment of autoimmune inflammatory rheumatic diseases, with perhaps enhanced efficacy and less toxicity than current therapies. Autologous hematopoietic stem cell transplants were the first foray into cellular therapies, with proven efficacy in scleroderma and multiple sclerosis...

BACKGROUND: Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. METHODS: Mice with scleroderma received a single 50 μg HUMSCs-Ex...

OBJECTIVE: To examine the potential therapeutic effect of mesenchymal stem cells (MSCs) for experimental scleroderma. MATERIALS AND METHODS: Fifty-four mice six-week-old (30-35 g) were studied. Hypochlorous acid (HOCl) induced scleroderma was considered. Mice were divided into 3 groups: (I) Control: Six mice did not receive any treatment and were sacrificed at the end of the experiment; (II) HOCl mice (induced scleroderma as a positive control): (III) MSCs-treated HOCl mice: Thirty six HOCl-induced mice were injected with MSCs (7...

Mesenchymal stem cells (MSCs) have become a promising therapeutic strategy for scleroderma. Exosomes derived from MSCs (MSC-exosomes) possess functional properties similar to those of their source cells. In this study, we aimed to explore the potential role of MSC-exosomes in the treatment of scleroderma. MSC-exosomes were isolated from human umbilical cords through ultracentrifugation and characterized. An experimental fibrosis model was established in BALB/c mice by a subcutaneous injection of bleomycin, followed by treatment with MSC-exosomes or MSC infusions once a week for a total of four doses...

Background and Objectives: Systemic scleroderma (SSc) is a rare and serious connective tissue disease, an autoimmune disease, and a rare refractory disease. In this study, preventive effect of single systemic human umbilical cord mesenchymal stem cells (UC-MSCs) transfusion on SSc was preliminarily explored. Methods and Results: SSc mouse model was established by daily intradermal injection of Hypochlorite (HOCl). SSc mice were treated by single transfusion of UC-MSCs at 0...

BACKGROUND: Systemic sclerosis (SSc) is a disease that features severe fibrosis of the skin and lacks effective therapy. Bone marrow mesenchymal stem cell (BMSC)-derived extracellular vesicles (EVs) are potential stem cell-based tools for the treatment of SSc. METHODS: BMSCs were isolated from the bone marrow of mice and identified with surface markers according to multilineage differentiation. EVs were isolated from the BMSC culture medium by ultracentrifugation and identified with a Nanosight NS300 particle size analyzer, transmission electron microscopy (TEM), and western blot...

Systemic sclerosis (SSc) is a potentially lethal disease with no curative treatment. Mesenchymal stromal cells (MSCs) have proved efficacy in SSc but no data is available on MSC-derived extracellular vesicles (EVs) in this multi-organ fibrosis disease. Small size (ssEVs) and large size EVs (lsEVs) were isolated from murine MSCs or human adipose tissue-derived MSCs (ASCs). Control antagomiR (Ct) or antagomiR-29a-3p (A29a) were transfected in MSCs and ASCs before EV production. EVs were injected in the HOCl-induced SSc model at day 21 and euthanasized at day 42...

Mesenchymal progenitor cells play a key role in fibrogenesis. An exciting paper was recently published showed that blister fluid from the skin patients with the autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc) preferentially activated mesenchymal progenitor cells (Taki et al. in Arthritis Rheumatol 72(8):1361-1374, 2020). These data provide new and invaluable insights into the complex interactions in the connective tissue microenvironment that ultimately result in persistent, pathological fibrosis...

INTRODUCTION: Sistemic Sclerosis (SSc) is a heterogeneous autoimmune disease with a high rate of progression and therapeutic failure, and treatment is a challenge, new therapeutic proposals being needed, being mesenchymal stem cells (MSCs) considered as alternative therapy for SSc for its immunomodulatory capacity. We evaluated the efficacy and safety of human MSC (hMSC) in patients with SSc through a systematic literature review (SLR). METHODS: SLR (PRISMA guideline) on MEDLINE/OVID, LILACS, EMBASE, and Cochrane/OVID bases (until July 2020, without limits)...

Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases...

OBJECTIVE: In prevous studies, we established a new animal model, KLF5+/- ;Fli-1+/- mice, in which fundamental pathologic features of systemic sclerosis (SSc) are broadly recapitulated. SSc vasculopathy is believed to occur as a result of impaired vascular remodeling, but its detailed mechanism of action remains unknown. To address this, the present study investigated the properties of dermal microvascular endothelial cells (DMECs), bone marrow-derived endothelial progenitor cells (BM-EPCs), and bone marrow-derived mesenchymal stem cells (BM-MSCs), a precursor of pericytes, in KLF5+/- ;Fli-1+/- mice...

AIM: Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. Although SSc has a high mortality risk, an effective treatment for the disease has not been established yet. Mesenchymal stromal/stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that have the ability to regulate immune responses. Adipose-derived stromal/stem cells (ASCs), one of the types of MSCs, have the advantage of accessibility and potent immunomodulatory effects when compared with other MSCs, such as bone marrow-derived MSCs...

Systemic sclerosis (SSc; scleroderma) is characterized by life-threatening progressive multiorgan fibrosis orchestrated by profibrotic myofibroblasts originating from different sources. Because recent data demonstrated that the majority of myofibroblasts in a murine scleroderma model arise from adipocytic progenitors through the adipocyte-myofibroblast transition process, we sought to determine whether the SSc microenvironment may affect the differentiation potential of adipose-derived stem cells (ADSC). Normal human ADSC from three donors were treated with serum from SSc patients ( n = 6), serum from healthy individuals ( n = 6), or recombinant human transforming growth factor-β1 (TGFβ1) as positive control of myofibroblastic phenotype induction...