Umbilical Cord Mesenchymal Stem Cells for Inhibiting the Fibrosis and Autoimmune Development in HOCl-Induced Systemic Scleroderma Mouse Model

Abstract

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 0.625×10 5 , 2.5×10 5 and 1×10 6 respectively. At the 42nd day of intradermal injection of HOCl, the symptoms showed up by skin and alveolar wall thickening, lymphocytic infiltration, increased collagen in skin/lung, and the increased proportion of CD3 FoxP3＋ cells (a Treg subset) in spleen. After UC-MSCs transfusion, the degree of skin thickening, alveolar wall thickening and lymphocyte infiltration were decreased, the collagen sedimentation in skin/lung was decreased, and the proportion of CD3 FoxP3＋ cells was decreased. Conclusions: UC-MSC can achieve a preventive effect in SSc mice by fibrosis attenuation and immunoregulation.

Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches

“…Subsequently, Yang et al documented improvements in cutaneous fibrosis after the infusion of umbilical cord-derived MSCs in the a bleomycin-induced SSc model, with decreased collagen synthesis and inhibition of Th-17 cell function [ 81 ]. Analogous results have been obtained in the HOCI-induced model, in which the elevated levels of plasmatic nitric oxide and of cutaneous/lung tissue α-SMA and TGF-β1 normalized after umbilical cord- or bone marrow-derived MSC infusions, reaching nearly a normal histopathology of lung and skin [ 82 , 83 , 84 ] Interestingly, also the administration of extracellular vesicles derived from MSCs primed with IFN-gamma has been demonstrated to improve lung-fibrosis in preclinical studies [ 85 , 86 ].…”

Mesenchymal Stem/Stromal Cell-Based Therapies in Systemic Rheumatic Disease: From Challenges to New Approaches for Overcoming Restrictions

“…In another animal model—a hypochlorite (HOCl)-SSc model—intravenous BM-MSC injection demonstrated therapeutic effects, including reduced skin and lung fibrosis, inflammation, and anti-Scl-70 autoantibodies [ 67 ]. UC-MSCs use in the HOCl-SSc model also prevented fibrosis [ 68 ]. Overall, preclinical studies conducted in SSc animal models have revealed the potential of MSCs in the involvement of the skin and lungs in SSc.…”