Article type: Research Article
Authors: Alexanian, Arshak R. | Kwok, Wai-Meng | Pravdic, Danijel | Maiman, Dennis J. | Fehlings, Michael G.
Affiliations: Neuroscience Research Labs, Deptpartment of
Neurosurgery, Medical College of Wisconsin, VAMC, Milwaukee, WI, USA | Department of Anesthesiology, and Department of
Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI,
USA | Department of Neurosurgery, Medical College of
Wisconsin, VAMC, Milwaukee, WI, USA | Department of Surgery, University of Toronto,
Neurosurgery, Toronto, Ontario, Canada
Note: [] Correspondence author: Arshak R. Alexanian, Ph.D, VMD,
Neuroscience Research Labs, Department of Neurosurgery, Medical College of
Wisconsin, VAMC, 5000 W. National Ave 151, Milwaukee, WI 53295, USA. Tel.: +1
414 384 2000 Ext. 41468; Fax: +1 414 384 3493; E-mail: aalexan@mcw.edu
Abstract: Purpose: We recently developed a new method for efficient generation
of neural-like cells from mice bone marrow (BM)-derived mesenchymal stem cells
(MSC) by exposing MSCs to epigenetic modifiers and a neural stem cell
environment. These neurally induced MSCs (NI-MSCs) differentiate into neuronal-
and glial-like cells in vitro, release neurotrophic factors NGF and BDNF,
survive and integrate after transplantation in intact spinal cord. The aim of
this study was to determine whether transplanted NI-MSCs survive,
differentiate, and integrate in injured spinal cord (ISC) rats and promote
functional recovery. Methods: Twenty rats, half grafted with MSCs and half with NI-MSCs,
were used for survival and differentiation studies. Results were analyzed using
triple-labeled immunohistochemistry. For motor function studies the 3 group of
adult female Sprague Dawley rats received PBS (vehicle), MSCs, or NI-MSCs,
respectively. Functional outcome was measured using the BBB scale. Results: Results demonstrated gradual improvement of locomotor
function in NI-MSC-transplanted rats in comparison to vehicle and non-modified
MSC-transplanted animals, with statistically significant differences at 7, 14,
and 21 days post transplantation. Immunocytochemical studies revealed poor
survival of NI-MSCs within the ISC as early as 3 weeks after
transplantation. Conclusions: Thus, there is a correlation between the degree of
surviving NI-MSCs and extent of functional recovery.
Keywords: Mesenchymal stem cells, neural cells, epigenetic, spinal cord, transplantation, survival, differentiation, regeneration
DOI: 10.3233/RNN-2010-0547
Journal: Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 761-767, 2010
Received 7 December 2010
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Accepted 7 December 2010
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Published: 2010
