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Round-the-clock imaging provides insight to intracellular macromolecular changes and sub- cellular localization.
Studies of stem cell expansion kinetics reveal that some adult stem cells have proliferation potential which is comparable to embryonic stem cells, and hence could generate large clinical cell doses.
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Live cell imaging (LCI) is a tool uniquely able to capture cell dynamics. LCI provides live viewing of the
behavior of a cell population in culture and allows us to obtain numerous real-time measurements at the
single cell level. The result is a detailed behavioral phenotype of the cell population which can be linked
to other in vitro analysis such as genomic or proteomic data or in vivo outcome measures. Here, we use
LCI to obtain novel comprehensive phenotype profiles and subsequently perform cytomic analysis and comparative
informatics on cell populations under various experimental conditions. Cytomics refers to the study of cell
phenotype and function.
Spatiotemporal changes in protein expression
A major focus of the Stem Cell Research Center and the McGowan Institute of Regenerative Medicine
is the translation of basic biology and engineering to clinical therapy. Temporal changes in gene
expression are being examined to elucidate basic molecular mechanisms. In one study, we are deciphering
the nature of a stem cell population by carefully examining all cell types in the population.
The overall goal is to understand how the subpopulations of a heterogeneous stem cell population work
together to create a niche which responds to injury and yet preserves the most potent cells in the population.
Stem Cell Expansion Kinetics
Bringing stem cells "from bench to bedside" and using them to regenerate damaged and lost tissue will require
the generation of large cell doses. It is also necessary to develop stem cell expansion methods to generate
the quantities of cells required to complete the basic studies. The 'natural' aging of the cells and their
in vitro expansion characteristics must be under-stood to ensure that the unavoidable cell culture manipulation
does not damage the therapeutic cells. Researchers at the LCI and the SCRC have found methods for the long-term
expansion of muscle derived stem cells.
Listed below are a sample of publications, abstracts and ongoing projects that utilize(d) this system.
Published reports
[1] Long-term self-renewal of postnatal muscle-derived stem cells. Deasy, B.M., B.M. Gharaibeh, J.B. Pollett, M.M. Jones, M.A. Lucas, Y. Kanda, and J. Huard. 2005. Mol Biol Cell. 16:3323-33.
[2] Nerve Growth Factor Improves the Muscle Regeneration Capacity of Muscle Stem Cells in Dystrophic Muscle. Lavasani, M., Lu, A., Peng, H., Cummins, J., Huard, J. (2005). Hum Gene Ther.
[3] Sex differences in muscle stem cells and in vivo muscle regeneration. Deasy, B.M., A. Lu, J.C. Tebbets, K. Urish, B.M. Gharabeih, B. Cao, R.T. Rubin, J. Cummins, and J. Huard. 2007. In review.
[4] Modeling stem cell population growth: incorporating terms for proliferative heterogeneity.Deasy, B.M., R.J. Jankowski, T.R. Payne, B. Cao, J.P. Goff, J.S. Greenberger, and J. Huard. 2003. Stem Cells. 21:536-45
[5] Mechanisms of muscle stem cell expansion with cytokines Deasy, B.M., Z. Qu-Peterson, J.S. Greenberger, and J. Huard. 2002.. Stem Cells. 20:50-60.
[6] The role of CD34 expression and cellular fusion in the regeneration capacity of myogenic progenitor cells Jankowski, R.J., B.M. Deasy, B. Cao, C. Gates, and J. Huard. 2002.. J Cell Sci. 115:4361-4374.
[7] Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. Qu-Petersen, Z., B. Deasy, R. Jankowski, M. Ikezawa, J. Cummins, R. Pruchnic, J. Mytinger, B. Cao, C. Gates, A. Wernig, and J. Huard. 2002. J Cell Biol. 157:851-64.
Published Abstracts (selected sample)
[1] Effect of Cytokines on the Non-exponential Proliferation of Stem Cells derived from Adult Skeletal Muscle. Deasy, B.M., Qu-Petersen, Z., Greenberger, J.S., and Huard, J. (2001) Biomedical Engineering Society Annual Meeting, Durham, North Carolina.
[2] Modeling Stem Cell Population Growth: Incorporating Parameters for Quiescence, Differentiation and Apoptosis Deasy, B.M, Jankowski R.J., Payne T.P., Greenberger J.S., and J.Huard. (2002)... 2nd Joint Meeting of IEEE Engineering in Medicine and Biology Society and Biomedical Engineering Society. Houston, Texas.
[3] Effects of uniaxial mechanical strain on muscle-derived stem cells. Corsi K, Huard J. (2005). 51st Annual Meeting of the Orthopaedic Research Society, Washington, D.C., USA.
[4] Characterization of Muscle Derived Stem Cells within a Novel Tissue Engineered Vascular Graft. Nieponice, A., Deasy, B.M. Soletti, L.,Guan, J., Huard, J., Wagner, W.R.,Vorp, D.A. (2005). Tissue Engineering Society International, December, Shangai, China.
On-going Collaborative Projects
[1] Cell migration, pseudopodia extension and cell growth on polymerized and nonpolymerized nanotube-coated surfaces. Collaborators at the McGowan Institute for Regenerative Medicine
[2] Hepatocyte cell growth. Collaborators at the Department of Pediatrics, University of Pittsburgh, Children's Hospital of Pittsburgh Rangos Research Center.
[3] Study of mesenchymal stem cell growth of various substrates and potential tissue engineering scaffolds. Collaborators at the McGowan Institute for Regenerative Medicine, Department of Bioengineering.
[4] Muscle-derived stem cell growth on tissue engineered vascular grafts. Collaborators at the McGowan Institute for Regenerative Medicine and Department of Bioengineering.
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