Bone Marrow Mesenchymal Stem Cells in Organ Repair and Strategies to Optimize their Efficacy

Bone marrow-derived mesenchymal stem cells (BMMSCs) are currently considered one of the cell types with great clinical potential for cell-based therapy. When transplanted systemically, mesenchymal stem cells (MSCs) are able to migrate to sites of injury and exert their therapeutic action via paracrine release of trophic factors instead of a direct repopulation of the damaged tissue. Experimental studies have reported the use of BMMSCs as preferred stem cells for therapy of acutely damaged heart, lung and liver. Some experimental studies using BMMSCs are translated into clinical trials, with results that are sometimes modest and controversial. Even in the kidney, stem cell therapy is approached to support the limited renal capacity to recover following acute ischemic or toxic injury. Acute kidney injury (AKI) is a potentially devastating disorder with an extremely serious outcome. Several pharmacological therapies for AKI are attempted with disappointing results. BMMSC therapy has been identified as a powerful treatment to regenerate damaged renal tissue in experimental models of AKI. To maximize treatment efficacy and translate these results to patients with highly compromised renal function, one needs to understand how to enhance the efficiency of MSCs in terms of migration, engraftment, production of cytokines and growth factors, and differentiation in the pathological environment of kidney failure. These issues are addressed in this chapter.