Bone Marrow Mesenchymal Stem Cells: From Characterization of Neural Differentiation to a Possible Therapeutic Use in Neurodegeneration

Bone marrow derived stromal cells are of mesenchymal origin and precursor cells for skeletal tissue components such as chondroblasts and osteoblasts. Furthermore, under experimental conditions, a differentiation potency into myogenic and neuronal cells could be demonstrated. Because of their multipotency these cells represent a population of non-haematogen stem cells that can be regarded as an alternative to human embryonic stem cells for future autologous cell replacement therapies. For a closer look at the differentiation capacity of these cells, rat and human bone marrow stromal cells were isolated from the femur bone and kept in the cell culture applying different cultivation protocols. In a cultivation medium with a serum content of 20%, the majority of these cells express a variety of neuronal markers such as ß-III Tubulin and NeuN as well as the astrocyte marker GFAP, while a minority of about 20% express the marker for neural precursor cells nestin. Cultivation in a chemically defined serum free medium results in the differentiation of a markedly higher percentage of nestin positive neural precursor-like cells. Using bFGF in combination with B27 these cells can be forced to form three dimensionally organized spheres. In order to elucidate a possible therapeutical potency of the bone marrow derived cells the synthesis of neurotrophic factors such as BDNF and NGF were analysed using the ELISA technique. Furthermore, they can be infected using a third generation adenoviral vector with high efficiency and show migratory activity in vitro . After injection of bone marrow derived mesenchymal stem cells into the lateral ventricle of adult rats they adhere to the ependymocytes and pass the ependymal barrier in order to settle in the subventricular space.