Adipose-Derived Cell Transplantation in Systemic Sclerosis: State of the Art and Future Perspectives

Abstract

REVIEW tation (HSCT) has demonstrated to be an effective treatment to cure some patients with severe autoimmune diseases (3), including scleroderma. After encouraging pilot studies showing beneficial effects of HSCT on immunomodulation, fibrosis and angiogenesis (4), controlled clinical trials definitively established HSCT as a true disease-modifying treatment of SSc (5, 6). Still, the transplant-related mortality that can reach 10%, and the not entirely negligible disease-progression rates after HSCT, indicate that further improvements have still to be researched. Multipotent mesenchymal stromal cells (MSCs) have been used in many animal and human studies as an attractive candidate for cell-based therapies. MSCs comprise a heterogeneous population of cells with multilineage differentiation potential that are preferentially able to home to the sites of damage, and secrete various cytokines and growth factors that can have immunomodulatory, angiogenic, anti-inflammatory and anti-apoptotic effects (7). From the clinical perspective, one of the most attractive properties of MSCs is their low immunogenicity, which allows their safe therapeutic application in allogeneic and even xenogeneic settings (7, 8). In terms of the source of MSCs, those derived from the bone marrow (BM) are the first and the most extensively characterized (9). BM-MSCs are currently used in the graft-versus-host-disease and have been tested in a variety of immune-mediated diseases (10-12). More recently, MSCs have been isolated from various other sources including adipose tissue (AT), umbilical cord

The Role of Endothelial Progenitors in the Repair of Vascular Damage in Systemic Sclerosis

“…To date, therapeutic mechanisms responsible for angiogenic properties of adipose tissue implantation have not been fully understood. It is likely that both the heterogeneous cellular mixture and growth factors may account for the robust angiogenic and vasculogenic potential confirmed in experimental and human studies ( 104 ).…”

“…The ability of SVF to promote angiogenesis and neovascularization has major implications for diseases characterized by poor vascularization, ischemia, and necrosis. Its application has resulted in neovascular formation when applied to acute myocardial infarction, cosmetic procedures, burn wounds, diabetic foot ulcers, and ischemic muscle ( 104 ). Prompted by these results, the simple autologous fat grafting (AFG) and other evolved procedures have been used for the treatment of SSc cutaneous complications, such as perioral changes and hand involvement, including skin fibrosis and ulcers ( 105 – 107 ).…”

Evidence-based management of Raynaud’s phenomenon

“…Autologous fat grafting or injection of adipose tissue derived stromal or stem cells 71,72 is now attracting substantial interest in SSc-related digital vasculopathy and at least one controlled trial is underway. Although the exact mechanism of action of fat grafting in this clinical context is not fully understood, it is likely that the transplanted cells have proangiogenic, antifibrotic, anti-inflammatory and immunomodulatory effects.…”

“…Although the exact mechanism of action of fat grafting in this clinical context is not fully understood, it is likely that the transplanted cells have proangiogenic, antifibrotic, anti-inflammatory and immunomodulatory effects. 71,72…”

Adipose-derived mesenchymal stromal/stem cells in systemic sclerosis: Alterations in function and beneficial effect on lung fibrosis are regulated by caveolin-1

“…In comparison with other sources, AT MSCs are more easily cultured, grow more rapidly, can be cultured for longer times before becoming senescent, and in many cases are more effective in treating disease. 3,4 MSCs have three key features important in their isolation, characterization, and potential use in the treatment of diseases: (1) adherence to standard tissue culture plastic; (2) specific surface antigens: MSCs are CD73+, CD90+, CD105+, and CD45-; and (3) they can differentiate into many cell types including adipocytes, osteocytes, chondrocytes, fibroblasts, and myocytes. 2 While MSC injection has beneficial effects on various diseases, it is unclear whether this is a direct effect (replacement of cell types) or an indirect effect (modulation of the tissue environment).…”