Mesenchymal stem cells: applications in cell and gene therapy

BOSCH, P.; STICE, S. L.

Frontiers of Cord Blood Science

Springer-Verlag

Lugar: London; Año: 2008; p. 99 - 124

Mesenchymal stem cells (MSCs) are one of the most extensively studied adult stem cells. These cells are believed to reside in tissues of mesenchymal origin particularly in the bone marrow but they have also been found in many other tissues including cord blood. Both in vivo and in vitro, these cells can differentiate down the adipogenic, chondrogenic, osteogenic lineages. MSCs also play an important role in hematopoiesis since they form part of the bone marrow microenvironment that promote hematopoietic stem cell proliferation and differentiation. In addition to the accepted orthodox plasticity of MSCs, several laboratories have reported a broader differentiation spectrum for MSCs including cell phenotypes from other embryonic germ layers such as neuron-like cells. Due to their stem cell nature, MSCs exhibit extensive proliferative potential in vitro (~40 cell doublings) while retaining multipotential differentiation capacity. Local administration of ex vivo expanded MSCs alone or in matrices has proven to be useful for treatment of bone and cartilage defects in a number of animal models and humans. Another approach envisions the use of genetically modified MSCs as in vivo mini-pumps for delivery of various therapeutic factors. The successful clinical applications of these and others MSC-based gene therapy approaches will depend greatly on our ability to efficiently deliver the gene of interest into MSCs. We will review the MSCs isolation, proliferation, differentiation and some of the therapeutic applications, alone and in combination with gene therapy.