NDLI: Improvement of neurological deficits in 6-hydroxydopamine-lesioned rats after transplantation with allogeneic simian virus 40 large tumor antigen gene-induced immortalized dopamine cells

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Improvement of neurological deficits in 6-hydroxydopamine-lesioned rats after transplantation with allogeneic simian virus 40 large tumor antigen gene-induced immortalized dopamine cells

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Improvement of neurological deficits in 6-hydroxydopamine-lesioned rats after transplantation with allogeneic simian virus 40 large tumor antigen gene-induced immortalized dopamine cells

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Edwards-prasad, J. Weiland, D. A. Clarkson, E. D. Rosa, F. G. Witta, S. E. Prasad, K. N. Freed, C. R.
Description	Author Affiliation: Clarkson ED ( Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.);
Abstract	The replacement of dopamine (DA) by DA neuron transplants in the treatment of advanced Parkinson disease (PD) is a rational approach. Because of limitations associated with fetal tissue transplants, a clone (1RB3AN27) of simian virus 40 large tumor antigen (LTa) gene-induced immortalized DA neurons were used in this study. These allogeneic immortalized dopamine neurons, when grafted into striata of normal rats, did not divide, did not form tumors, did not produce LTa, did not extend neurites to host neurons, and were not rejected, for as long as 13 months after transplantation. Grafted cells when recultured in vitro resumed cell proliferation and LTa production, suggesting the presence of a LTa gene-inhibiting factor in the brain. The grafting of undifferentiated and differentiated 1RB3AN27 cells or differentiated murine neuroblastoma (NBP2) cells into striata of 6-hydroxydopamine-lesioned rats (an animal model of PD) caused a time-dependent improvement in neurological deficits (reduction in the methamphetamine-induced turning rate). At 3 months after transplantation, 100% of the animals receiving differentiated 1RB3AN27 cells, 63% of the animals receiving undifferentiated 1RB3AN27 cells, 56% of the animals receiving differentiated NBP2 cells, and 0% of the sham-transplanted animals showed improvements in neurological deficits. At 6 months after transplantation, there was a progressive increase in spontaneous recovery in sham-transplanted animals. These results suggest that immortalized DA neurons should be further studied for their potential use in transplant therapy in advanced PD patients.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	3
Volume Number	95
Language	English
Publisher	National Academy of Sciences
Publisher Date	1998-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Polyomavirus Transforming Genetics Dopamine Physiology Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins Neurons Transplantation Virology Oxidopamine Toxicity Animals Carrier Proteins Metabolism Cell Differentiation Cells, Cultured Corpus Striatum Drug Effects Dopamine Plasma Membrane Transport Proteins RNA, Messenger Rats, Sprague-Dawley Simian Virus 40 Immunology Tyrosine 3-Monooxygenase Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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