Induction of neurotrophin expression via human adult mesenchymal stem cells: implication for cell therapy in neurodegenerative diseases.
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 (NGFR(p75)) 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.
Pisati
Federica
F
Fondazione IRCCS Ospedale Maggiore, Department of Neurological Sciences, Stem Cell Laboratory, Dino Ferrari Center, University of Milan, Milan, Italy.
Bossolasco
Patrizia
P
Meregalli
Mirella
M
Cova
Lidia
L
Belicchi
Marzia
M
Gavina
Manuela
M
Marchesi
Chiara
C
Calzarossa
Cinzia
C
Soligo
Davide
D
Lambertenghi-Deliliers
Giorgio
G
Bresolin
Nereo
N
Silani
Vincenzo
V
Torrente
Yvan
Y
Polli
Elio
E
D000328:Adult; D000818:Animals; D001921:Brain / Q000601:surgery; D002454:Cell Differentiation; D005455:Fluorescent Antibody Technique; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009414:Nerve Growth Factors / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000628:therapy*; D020933:Neurotrophin 3 / Q000378:metabolism; D009924:Organ Culture Techniques; D014183:Transplantation, Heterologous
D009414:Nerve Growth Factors; D020933:Neurotrophin 3