Impact of ageing on biological features of bone marrow stromal cells (BMSC) in cell transplantation therapy for CNS disorders: functional enhancement by granulocyte-colony stimulating factor (G-CSF).

ABSTRACT

This study was designed to clarify the effects of donor age on biological features of bone marrow stromal cells (BMSC), one of the candidates for cell transplantation therapy for CNS disorders, because many aged patients might require such therapy. This study was also aimed to test whether ex vivo treatments with granulocyte-colony stimulating factor (G-CSF) could modify biological properties of BMSC from aged donors and enhance its therapeutic effects in an animal model of traumatic brain injury. The BMSC were harvested from young (6-week-old) and aged (100-week-old) rats. The ageing significantly increased the senescence-associated ß-galactosidase (SA-ß-gal) activity of the cultured BMSC, and decreased their proliferative capacity and production of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). As the next step, the rats were subjected to brain freezing injury by applying liquid nitrogen onto the neocortex through the thinned skull. The 6-week BMSC, 100-week BMSC, G-CSF-treated 100-week BMSC or vehicle were stereotactically injected into the ipsilateral striatum at 7 days post-injury. Transplantation of the 6-week BMSC, but not 100-week BMSC, significantly improved locomotor function. However, treatment of the 100-week BMSC with 0.1 µmol of G-CSF significantly improved their proliferation activity and growth factor production, and recovered therapeutic effects in the injured brain. In conclusion, donor age may largely determine biological aspects of BMSC. G-CSF may contribute to improve the outcome of BMSC transplantation therapy for CNS disorders in aged patients.