Mesenchymal stem cells in the treatment of ischemic stroke: progress and possibilities.

Stroke is a major cause of death and long-term disability in industrialized countries, and the only causal therapy for stroke comprises recombinant tissue plasminogen activator(rt-PA)-mediated recanalization of the occluded vessel. New experimental strategies focus on neuroregenerative approaches, among which the application of mesenchymal stem cells (MSCs) has gained increasing attention. MSCs, like other stem cells, have the capacity of unlimited self-renewal giving rise to differentiated cells from various cell lineages. Bone marrow (BM)-derived MSCs are the most frequently used MSC type in experimental stroke studies. Application of BM-derived MSCs and, in some studies, transplantation of MSCs from other tissue sources resulted in an improved functional recovery in experimental animals, although stroke volumes were not always affected by MSC transplantation. The underlying precise mechanisms of this phenomenon remain elusive, although MSC transplantation is considered to affect many diverse events, eg, by modulating the inflammatory milieu, stimulating endogenous neurogenesis and angiogenesis, and reducing glial scar formation. On the contrary, neuronal differentiation and integration of transplanted MSCs do not seem to affect stroke outcome significantly. On the basis of these preclinical studies, first clinical trials confirmed improved functional recovery in patients who had received BM-derived MSCs systemically, although the number of patients enrolled in these studies was low and there were no adequate control groups. In this review, we describe some fundamental biological characteristics of MSCs and further review some preclinical experimental studies, with special emphasis on BM-derived MSCs. We also review clinical trials in which MSCs have been used and conclude with a short outlook on the application of MSCs in stroke research.