MESENCHYMAL STROMAL CELLS FOR SYSTEMIC SCLEROSIS TREATMENT
- Dominique Farge, France
Abstract
Background and Aims
Systemic sclerosis (SSc) is an orphan autoimmune disease characterized by vasculopathy, dysregulation of the immune response, and progressive fibrosis, with patients high morbidity and mortality. Mesenchymal stromal cells (MSC), demonstrating in vitro and in vivo pro-angiogenic, immuno-suppressive, and anti-fibrotic properties, appear a promising stem cell therapy for SSc. This work review how MSC can target SSc key pathological features.
Methods
An extensive literature analysis was based on combined clinical and immunological expertise on systemic sclerosis and on MSC characterization, production and evaluation of their functional properties
Results
MSC, defined by the International Society for Cellular Therapy, show in vitro and in vivo properties which vary according to the donor type (allogeneic or autologous), the tissue sources (bone marrow, adipose tissue or umbilical cord) and the recipient inflammatory micro-environment. Preclinical studies in SSc animal models show reduced skin and lung fibrosis after MSC infusion. First reports of MSC infusion in SSc patients show safety and early efficacy, which results are currently tested in several ongoing clinical trials worldwide.
Conclusions
To increase the success of MSC based clinical trials in SSc, the design and validation of relevant preclinical models and potency assays with good predictive value are required, with adequate clinical study design, based on immune profiling strategies allowing patient screening and follow-up. Ongoing studies will help establish the appropriate choice of MSC source in different clinical settings, optimal MSC characteristics and priming, as well as the method of delivery.