Bone Marrow-Derived Mesenchymal Stem Cells Promote Neuronal Networks with Functional Synaptic Transmission After Transplantation into Mice with Neurodegeneration
Article first published online: 1 MAY 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 5, pages 1307–1316, May 2007
How to Cite
Bae, J.-S., Han, H. S., Youn, D.-H., Carter, J. E., Modo, M., Schuchman, E. H. and Jin, H. K. (2007), Bone Marrow-Derived Mesenchymal Stem Cells Promote Neuronal Networks with Functional Synaptic Transmission After Transplantation into Mice with Neurodegeneration. STEM CELLS, 25: 1307–1316. doi: 10.1634/stemcells.2006-0561
- Issue published online: 2 JAN 2009
- Article first published online: 1 MAY 2007
- Manuscript Accepted: 25 JAN 2007
- Manuscript Received: 4 SEP 2006
- Neural network by stem cells
Recent studies have shown that bone marrow-derived MSCs (BM-MSCs) improve neurological deficits when transplanted into animal models of neurological disorders. However, the precise mechanism by which this occurs remains unknown. Herein we demonstrate that BM-MSCs are able to promote neuronal networks with functional synaptic transmission after transplantation into Niemann-Pick disease type C (NP-C) mouse cerebellum. To address the mechanism by which this occurs, we used gene microarray, whole-cell patch-clamp recordings, and immunohistochemistry to evaluate expression of neurotransmitter receptors on Purkinje neurons in the NP-C cerebellum. Gene microarray analysis revealed upregulation of genes involved in both excitatory and inhibitory neurotransmission encoding subunits of the ionotropic glutamate receptors (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, AMPA) GluR4 and GABAA receptor β2. We also demonstrated that BM-MSCs, when originated by fusion-like events with existing Purkinje neurons, develop into electrically active Purkinje neurons with functional synaptic formation. This study provides the first in vivo evidence that upregulation of neurotransmitter receptors may contribute to synapse formation via cell fusion-like processes after BM-MSC transplantation into mice with neurodegenerative disease.
Disclosure of potential conflicts of interest is found at the end of this article.