Research Interests
Research in my laboratory is focused on examining the biological nature of mesenchymal stem cells (MSCs) and evaluating their efficacy as cellular vectors to treat disease. In the former case, our laboratory has employed serial analysis of gene expression (SAGE) to catalog the entire repertoire of expressed transcripts in both human and murine MSCs. Interrogation of these SAGE databases has enabled us to identify signaling pathways that regulate MSC self-renewal and multi-cellular differentiation. It has also spurred the identification of various MSC subpopulations that express anti-inflammatory, neuro-regulatory, angiogenic and other regulatory proteins. Efforts are underway to characterize these subpopulations. Additionally, our laboratory has developed a reliable method to isolate murine MSCs from bone marrow using immunodepletion. Accordingly, this has provided the opportunity to evaluate the therapeutic efficacy of MSCs in various mouse models of disease. Specifically, we have focused on using the cells to treat chronic lung disease as well as disorders of the central nervous system. In the latter case, studies in mice have spurred a pre-clinical trial in Rhesus macaques to evaluate the safety and efficacy of direct intracranial MSC transplantation to treat neurologic sequelae associated with lysosomal storage diseases.
Selected Publications
Isakova IA, Baker K, Dufour J, Gaupp D, Phinney DG. Dose and age-related effects on MSCs engraftment levels and anatomical distribution in the CNS of non-human primates: Identification of novel MSC subpopulations that respond to guidance cues in brain. Stem Cells 2007; 25:3261-3270.
Phinney DG. Biochemical heterogeneity of mesenchymal stem cell populations: clues to their therapeutic efficacy. Cell Cycle 2007; 6:2884-2889.
Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, Phinney DG. Interleukin 1 receptor antagonist mediates the anti-inflammatory and anti-fibrotic effect of mesenchymal stem cells during lung injury. Proc. Natl. Acad. Sci. USA 2007; 104:11002-11007.
Kang KS, Yeo JE, Kang KS, Phinney DG. Cytoplasmic extracts from adipose tissue stromal cells alleviates secondary damage by modulating apoptosis and promotes functional recovery following spinal cord injury. Brain Pathology 2007; 17:263-275.
Phinney DG and Prockop DJ. The state of transdifferentiation and modes of tissue repair: current views. Stem Cells 2007; 25:2896-2902.
Phinney DG, Hill K, Michelson C, DuTreil M, Hughes C, Humphries S, Wilkinson R, Baddoo M, Bayly E. Biological activities encoded by the murine mesenchymal stem cell transcriptome provide a basis for their developmental plasticity and broad clinical eficacy. Stem Cells 2006; 24:186-198.
Isakova IA, Baker K, Dufour J, Gaupp D, Phinney DG. Pre-Clinical evaluation of adult stem cell engraftment and toxicity in the CNS of Rhesus Macaques. Mol. Therapy 2006; 13:1173-1184.
Phinney DG. Chapter 3. Gene expression profiles of mesenchymal stem cells, 2006; pp. 59-80 in Genetic Engineering of Mesenchymal Stem Cells, Edited by J. A. Nolta, Springer, P.O. Box 17, 3300 AA Dordrecht, The Netherlands.
Baddoo M, Hill K, Wilkinson R, Gaupp D, Hughes C, Kopen GC, Phinney DG. Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. J. Cell. Biochem. 2003; 89:1235-1249.
Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc. Natl. Acad. Sci. USA 2003; 100:8407-8411.
Contact: dphinne@tulane.edu