Induction of Neurotrophin Expression via Human Adult Mesenchymal Stem Cells: Implication for Cell Therapy in Neurodegenerative Diseases

Cell Transplantation

Article

Cinzia Calzarossa¹  Lidia Cova¹  Vincenzo Silani¹  Mirella Meregalli²  Marzia Belicchi²  Manuela Gavina²  Federica Pisati²  Nereo Bresolin²  Chiara Marchesi²  Yvan Torrente²  Elio Polli³  Patrizia Bossolasco³  Giorgio Lambertenghi-Deliliers⁴  Davide Soligo⁴ 

[1] Department of Neurology and Laboratory of Neuroscience, Dino Ferrari Center, University of Milan-Medical School, IRCCS Istituto Auxologico Italiano, Milan, Italy;Fondazione IRCCS Ospedale Maggiore, Department of Neurological Sciences, Stem Cell Laboratory, Dino Ferrari Center, University of Milan, Milan, Italy;Fondazione Matarelli, Ospedale Fatebenefratelli e Oftalmico, Laboratory of Matarelli Foundation for Blood Diseases, Milan, Italy;Fondazione Matarelli, Ospedale Fatebenefratelli e Oftalmico, Laboratory of Matarelli Foundation for Blood Diseases, Milan, Italy;Fondazione IRCCS Ospedale Maggiore, Bone Marrow Transplantation Center, University of Milan-Medical School, Milan, Italy;

关键词: Mesenchymal stem cells;    Transplantation;    Neurotrophin;    Astroglial cells;   

DOI  :  10.3727/000000007783464443

 received in 2006-06-03, accepted in 2006-09-05,  发布年份 2007

来源: Sage Journals

【 摘 要 】

In animal models of neurological disorders for cerebral ischemia, Parkinson's disease, and spinal cord lesions, transplantation of mesenchymal stem cells (MSCs) has been reported to improve functional outcome. Three mechanisms have been suggested for the effects of the MSCs: transdifferentiation of the grafted cells with replacement of degenerating neural cells, cell fusion, and neuroprotection of the dying cells. Here we demonstrate that a restricted number of cells with differentiated astroglial features can be obtained from human adult MSCs (hMSCs) both in vitro using different induction protocols and in vivo after transplantation into the developing mouse brain. We then examined the in vitro differentiation capacity of the hMSCs in coculture with slices of neonatal brain cortex. In this condition the hMSCs did not show any neuronal transdifferentiation but expressed neurotrophin low-affinity (NGFRp75) and high-affinity (trkC) receptors and released nerve growth factor (NGF) and neurotrophin-3 (NT-3). The same neurotrophin's expression was demonstrated 45 days after the intracerebral transplantation of hMSCs into nude mice with surviving astroglial cells. These data further confirm the limited capability of adult hMSC to differentiate into neurons whereas they differentiated in astroglial cells. Moreover, the secretion of neurotrophic factors combined with activation of the specific receptors of transplanted hMSCs demonstrated an alternative mechanism for neuroprotection of degenerating neurons. hMSCs are further defined in their transplantation potential for treating neurological disorders.

【 授权许可】

Unknown   
© 2007 Cognizant Comm. Corp.