In-vitro differentiative potential of MSCs is not restricted
to mesodermal lineages, but their transdifferentiation into other lineages, such as endothelia, could be realized Doxorubicin both in vitro and in vivo . In addition, MSCs exhibit immunoregulatory activities, inhibiting the function of different immune cells of innate and adaptive immunity , blocking the division of stimulated T cells, preventing irreversible G0/G1 phase arrest and stopping T cell division in mixed lymphocyte reactions (MLRs) . However, the immunomodulatory activity of the MSCs does not rely solely upon T cells, but also upon the first step of the immune response through the inhibition of dendritic cell differentiation and maturation in antigen-presenting cells . Furthermore, their regulatory activity may be amplified by modulating immune responses via the de-novo induction and expansion of CD4+CD25+forkhead box protein 3 (FoxP3)+ regulatory T cells (Tregs). Tregs play a critical role in peripheral self-tolerance, as well as in the regulation of acquired immunity, by inhibition of lymphocyte proliferation [9, 10]. As well as Tregs developing in the
thymus (natural Tregs), a Treg population can be induced from peripheral naive STA-9090 purchase T cell (inducible Tregs), and these inducible Tregs can be recruited directly by MSC from CD4+ T cells [11, 12]. In recent decades many studies have been published addressing the role of Treg number and function in human autoimmunity , suggesting that their possible defective function plays a role in many autoimmune diseases. On this basis, both the regenerative and the immunomodulatory properties of MSCs make them an attractive candidate Thalidomide for cellular therapy in autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease in which alteration of cellular immunity, including T and B lymphocytes, has been largely
studied both in the skin and in internal organs [14, 15]. Furthermore, recent evidence has shown an aberrant dendritic cell function in SSc, contributing to the molecular milieu of the disease . We have shown previously that MSCs obtained from SSc patients (SSc–MSC) were normal with respect to clonogenicity and differentiative capacity, although they displayed early senescence and were defective in acquiring some differentiative functions . Senescent MSC generally show a flattened morphology, over-expression of senescence-associated β-galactosidase (β-Gal) activity, reduced telomerase activity and increased expression of both p53 and p21, which are negative regulators of cell proliferation . At present, only few papers have investigated the immunoregulatory activity in SSc.