Systemic sclerosis is also an autoimmune systemic disease, characterized by inflammation and vascular hyperreactivity of the microcirculation and macrocirculation associated with excessive deposition of collagen in the tissues, resulting in fibrosis in the skin and in internal organs (187). Clinically, the disease is characterized by inflammatory, fibrotic and atrophic alterations, along with proliferative endarteritis and obstructive capillary lesions compromising the skin, musculoskeletal system and internal organs, particularly the heart, kidneys, lungs and gastrointestinal tract (188). The main cause of death from systemic sclerosis is related to its pulmonary involvement, which often results in pulmonary hypertension. The exacerbate production of the cytokines IL-4 and IL-13 is a result of the activation of T cells by antigens and the subsequent induction of a Th2 response, which stimulates the process of fibrosis (189). Autoantibodies are also produced in high quantities due to the activation of B cells, which adopts a profibrotic phenotype. Finally, macrophages in perivascular infiltrates are also activated, leading to the production of CCL2, TGF-β, and platelet-derived growth factor (PDGF), all of which promote fibrosis and fibroproliferation (190). Only one (85) of the studies analyzed applied hMSCs for the treatment of systemic sclerosis. This study was conducted in humans and used the umbilical cord as the source of hMSCs. In this study, the primary study endpoints used were: the modified Rodnan skin score; and variables associated with interstitial lung disease such as the diffusing capacity of the lung for carbon monoxide and the forced vital capacity. The serum levels of TGF-β, VEGF and anti-SCL70 IgG antibody were used as additional study endpoints as they provide a strong evidence of the efficacy of the therapy in modulating autoimmunity and decreasing the levels of profibrotic mediators. The modified Rodnan skin score is the primary endpoint used almost universally in systemic sclerosis clinical trials. However, the Rodnan skin score does not describe the progression of the disease across multiple organ systems and is vulnerable to observation bias in single-arm open label trials as this method is based on interpretation by both physicians and patients. Therefore, we propose that the disease-free survival rate should be considered the most appropriate primary endpoint in clinical trials to assess the effectiveness of hMSCs administration for the treatment of systemic sclerosis as this endpoint is able to identify the occurrence of the disease in multiple organs and is less vulnerable to bias. Furthermore, exploratory endpoints such as the serum level of TGF-β and PDGF should used in conjunction with the primary endpoint selected in order to allow the researchers to assess the efficacy of the hMSCs administration in modulating autoimmunity. The study selected demonstrated that the administration of hMSCs resulted in an improvement in both the modified Rodnan Skin Score and lung function. Furthermore, a decrease in the serum levels of inflammatory markers and profibrotic mediators such as TGF-β and VEGF and in level of the anti-Scl70 autoantibody was also observed during follow up. Table 3 summarizes the methodology employed and the results obtained in the studies selected in this systematic review regarding the effects of the administration of hMSCs for the treatment of systemic lupus erythematosus and systemic sclerosis.