Methodology, biology and clinical applications of human mesenchymal stem cells.

Stem cells are known by their capacity of self-renewal and differentiation into at least one specialized cell type. Mesenchymal stem cells (MSCs) were isolated initially from bone marrow but are now known to exist in any vascularized organ or tissue in adults. MSCs have a great therapeutic potential, due to their ability to migrate to sites of tissue injury and secrete trophic factors that hasten endogenous repair. They have also been shown to present immunosuppressive properties that may be used in the treatment of autoimmune or graft-versus-host diseases. Clinical trials employing MSCs show that the therapy is safe, but the efficiency needs to be in tested in phase III and IV studies. We describe here protocols for the isolation of human MSCs from human bone marrow and adipose tissue. The safe use of these cells demand a thorough in vitro characterization, as described in protocols of immunophenotyping by flow cytometry and analysis of their capacity to differentiate into adipogenic, osteogenic, and chondrogenic lineages.

In situ delivery of bone marrow cells and mesenchymal stem cells improves cardiovascular function in hypertensive rats submitted to myocardial infarction.

This work aimed to evaluate cardiac morphology/function and histological changes induced by bone marrow cells (BMCs) and cultured mesenchymal stem cells (MSCs) injected at the myocardium of spontaneously hypertensive rats (SHR) submitted to surgical coronary occlusion. Female syngeneic adult SHR, submitted (MI) or not (C) to coronary occlusion, were treated 24 h later with in situ injections of normal medium (NM), or with MSCs (MSC) or BMCs (BM) from male rats. The animals were evaluated after 1 and 30 days by echocardiography, histology of heart sections and PCR for the Y chromosome. Improved ejection fraction and reduced left ventricle infarcted area were observed in MSC rats as compared to the other experimental groups. Treated groups had significantly reduced lesion tissue score, increased capillary density and normal (not-atrophied) myocytes, as compared to NM and C groups. The survival rate was higher in C, NM and MSC groups as compared to MI and BM groups. In situ injection of both MSCs and BMCs resulted in improved cardiac morphology, in a more physiological model of myocardial infarction represented by surgical coronary occlusion of spontaneously hypertensive rats. Only treatment with MSCs, however, ameliorated left ventricle dysfunction, suggesting a positive role of these cells in heart remodeling in infarcted hypertensive subjects.