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TISSUE-SPECIFIC STEM CELLS

Bone Marrow-Derived Mesenchymal Stem Cells Promote Neuronal Networks with Functional Synaptic Transmission After Transplantation into Mice with Neurodegeneration

Departments of ^aPhysiology, College of Medicine,
^dOral Physiology, School of Dentistry and Brain Korea 21,
^gLaboratory Animal Medicine, College of Veterinary Medicine, and
^cStem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea;
^bDepartment of Mental Health Sciences, Royal Free and University College Medical School, University College London, London, United Kingdom;
^eNeuroimaging Research Group P042, Department of Neurology, Institute of Psychiatry, King's College London, London, United Kingdom;
^fDepartment of Human Genetics and Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York, USA

Key Words. Neural network by stem cells

Correspondence: Hee Kyung Jin, D.V.M., Ph.D., College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. Telephone: 82-53-950-5966; Fax: 82-53-950-5955; e-mail: hkjin{at}mail.knu.ac.kr

Received September 4, 2006; accepted for publication January 25, 2007.


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 (-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, AMPA) GluR4 and GABA_A 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.