Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue?

Patients with systemic lupus erythematosus (SLE) remain at increased risk for premature death [1], particularly among young adults [2]. Up to 45% of cases present early end organ damage, related to persistent activity or kidney disease [3]. Renal involvement, which occurs in 40 to 50% of patients in most series, is associated with mortality rates approximately eight times higher than expected [2], and remains only partially responsive to the best available treatments. Indeed, therapy with cyclophosphamide has not improved patient survival compared with corticosteroids [4], and the largest controlled trial comparing mycophenolate mofetil with intravenous cyclophosphamide in lupus nephritis achieved complete remission in only 8.6% and 8.1% of patients, respectively [5]. Undoubtedly there is a need for safer and more effective treatments for SLE.Mesenchymal stromal cells, originally described in the 1960s as bone forming cells in the bone marrow [6], are now called multipotent mesenchymal stromal cells, or more commonly mesenchymal stem cells (MSCs) since they display adult stem cell multipotency. Thus, they differentiate into bone, cartilage and other connective tissues [7]. Unlike hematopoietic stem cells, which originate from bone marrow, MSCs can also be isolated from a variety of other tissues, such as umbilical cord or adipose tissue, and can be extensively expanded in vitro by up to 50 cell doublings without differentiation [8]. While these properties initially put MSCs center stage of an alleged era of regenerative medicine, the unexpected findings of Bartholomew and colleagues in 2002 [9] pointed to new features of these progenitor cells, the consequences of which are still being revealed in several areas of medicine. MSCs were found to escape T-cell recognition, suppress T-cell response to mitogens and also to prolong skin graft survival in baboons. In spite of a wide array of immunomodulatory effects that were subsequently proven to affect T and B lymphocyte