Epigenetic conversion of human adult bone mesodermal stromal cells into neuroectodermal cell types for replacement therapy of neurodegenerative disorders

Abstract

Tissue-specific stem cells, such as bone marrow-derived mesodermal stromal cells (MSCs), are thought to be lineage restricted and, therefore, could only be differentiated into cell types of the tissue of origin. Several recent studies, however, suggest that these types of stem cells might be able to break barriers of germ layer commitment and differentiate in vitro and/or in vivo into cells of different tissues, such as neuroectodermal cell types. Recently, protocols for high-yield generation of undifferentiated neural stem cell (NSC)-like cells from MSCs of primate and human origin were reported. Undifferentiated NSCs are commonly used and are more suitable for neurotransplantation compared with fully differentiated neural cells, as differentiated neural cells are well known to poorly survive detachment and subsequent transplantation procedures. These human MSC-derived NSC-like cells (MSC-NSCs) grow in neurosphere-like structures and express high levels of early neuroectodermal markers, but lose characteristics of MSCs. In the presence of selected growth factors, human MSC-NSCs can be differentiated into the three main neural phenotypes: astroglia, oligodendroglia and neurons. Compared with direct differentiation of human MSCs into mature neural cells, the conversion step seems to be essential to generate mature functional neuroectodermal cells. This review describes the techniques for the conversion of human MSCs into NSCs and summarises the data on epigenetic conversion of human MSCs into immature neuroectodermal cells. These cells provide a powerful tool for investigating the molecular mechanisms of neural differentiation, and might serve as an autologous cell source to treat acute and chronic neurodegenerative diseases.

Keywords::

• bone marrow cells
• mesodermal stromal cells
• neural stem cells
• neurodegenerative disease transplantation

Acknowledgements

The work of the authors was supported in part by the Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Ulm (Project D6), the BMBF (Cooperation Programme ‘Tissue Engineering’ [AZ 0312126] and the Polish-German Cooperation in Neuroscience Programme [01GZ0313]), and the Landesstiftung Baden-Württemberg (Förderprogramm ‘Adulte Stammzellen’; AZ 37610). AH was supported by an IZKF fellowship, as member of the graduate college GRK460, Ulm.