This proposal intends to explore the therapeutic potential of human bone marrow derived multipotent adult stem cells (MAPCs) for neural transplantation and repair. MAPCs could provide a (1) source of grafting tissue for cell replacement therapies and (2) gene therapy vehicles to correct metabolic or neurochemical deficiencies in the CNS. We will test whether human MAPCs can migrate and undergo neuronal, site-specific differentiation in vivo by transplanting them into neonatal rats. Since cholinergic basal forebrain degeneration is correlated with cognitive decline in Alzheimer?s disease, we will particularly addresss the potential for cholinergic differentiation of MAPCs when transplanted in this region. Ex-vivo nerve growth factor gene transfer has been shown to be a suitable approach to improve the cognitive deficits associated with degeneration of the basal forebrain cholinergic system, as seen in aging and Alzheimer?s disease. As gene therapy vehicles, we are interested in determining the effectiveness of NGF-secreting MAPCs transplants to ameliorate the cognitive deficits of animals with partial cholinergic immunolesions. Therefore, our experiments will test the role for MAPCs as a readily available source for neural transplantation tissue that besides the advantage of being amenable to expansion, differentiation and genetic manipulation in vitro, also embodies the unique prospect for autologous transplantation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS043121-04
Application #
6896129
Study Section
Special Emphasis Panel (ZRG1-RPHB-3 (20))
Program Officer
Refolo, Lorenzo
Project Start
2002-05-01
Project End
2006-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
4
Fiscal Year
2005
Total Cost
$36,122
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455