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

Abstract

Systemic sclerosis (SSc) is a systemic disease characterized by autoimmune responses, vasculopathy and tissue fibrosis. The pathogenic mechanisms involve a wide range of cells and soluble factors. The complexity of interactions leads to heterogeneous clinical features in terms of the extent, severity, and rate of progression of skin fibrosis and internal organ involvement. Available disease-modifying drugs have only modest effects on halting disease progression and may be associated with significant side effects. Therefore, cellular therapies have been developed aiming at the restoration of immunologic self-tolerance in order to provide durable remissions or to foster tissue regeneration. Currently, SSc is recommended as the ‘standard indication’ for autologous hematopoietic stem cell transplantation by the European Society for Blood and Marrow Transplantation. This review provides an overview on cellular therapies in SSc, from pre-clinical models to clinical applications, opening towards more advanced cellular therapies, such as mesenchymal stem cells, regulatory T cells and potentially CAR-T-cell therapies.

Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers

“…The concept of CARs was first described over 25 years ago by Gross et al and has been improved upon over time [ 231 ]. Today, the technique is being studied in various autoimmune connective tissue conditions [ 232 ], holding promise for the potential treatment of SSc [ 233 ]. Furthermore, the use of CAR-T-cell (CAR-T) therapy in BCC resulted in partial tumor regression [ 234 ].…”

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

“…Despite high safety, polyclonal Tregs mediated suboptimal/controversial responses in clinical trials, 24 , 25 , 26 , 27 which was mainly attributed to low amount of disease relevant, antigen-specific cells ( Supplementary Table S2 ). 28 , 29 , 30 , 31 …”