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1615 Poydras Street - Suite 1000
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Areas of Research: Adult Stem Cells as Therapeutic Vectors Research by Dr. Phinney is focused on examining marrow stromal stem cells (MSC) via the use of serial analysis of gene expression (SAGE) to catalog their entire repertoire of expressed transcripts. The SAGE technology is the first technology that makes it possible to measure all the genes expressed by a cell. The data obtained with SAGE are being used to discover factors that regulate MSC self-renewal and differentiation and to identify reliable markers to isolate the cells. Concurrently, Dr. Phinney’s laboratory is evaluating the efficacy of MSC as cellular vectors to treat genetic diseases of bone, idiopathic pulmonary fibrosis, and neurodegenerative diseases of the central nervous system (CNS). A pre-clinical study is underway using rhesus macaques to evaluate the safety of using MSC as therapeutic vectors. In these studies, male donor MSCs from specific pathogen-free animals are injected directly into the CNS of infant or young adult female macaques using stereotactic coordinated determined from magnetic resonance imaging of the brain. At various times post-transplant the health, spontaneous behavior, postural and locomotor function and fine motor performance of each transplant recipient is evaluated. These data are then correlated with the levels and anatomical distribution in brain of engrafted MSCs. To date, these studies have demonstrated that engrafted MSCs persist in the brain from at least 6 months post-injection and localize to specific anatomical regions along the neuraxis including the hippocampus and cerebellum. No adverse affects on animal health, behavior or motor performance have been associated with MSC engraftment. Therefore, the results indicate that MSC-based approaches may provide a safe alternative to treating various CNS diseases that are intractable to standard therapies. Selected Publications Phinney, D.G., and Isakova, I. Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Current Pharmaceutical Design, (2005) 11(10): 1255-1265 Phinney, D.G., Hill, K., Michelson, C., Humphries, S., Wilkinson, R., and Baddoo, M. Biological activities encoded by the murine mesenchymal stem cell transcriptome provide a basis for their developmental plasticity and broad clinical efficacy. Stem Cells, (2005) Crigler, L., Robey, R.C., Asawachaicharn, A., Gaupp, D., and Phinney,
D.G. Human mesenchymal stem cells express a variety of neuro-regulatory
molecules and promote neuronal cell survival and neuritogenesis.
Experimental Neurology, (2005) Isakova, I., Baker, K., Dufour, J., Gaupp, D., and Phinney, D.G. Pre-clinical evaluation of adult stem cell engraftment and toxicity in the CNS of rhesus macaques. Molecular Therapy (2005) Phinney, D.G., Baddoo, M., Gaupp, D., DuTreil, M., and Isakova, I. Murine MSCs transplanted to the CNS of neonatal vs. adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration. Stem Cell and Development, (2005) |
Donald Phinney, PhD