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dc.contributor.advisorJames L. Sherley.en_US
dc.contributor.authorGanz, Michalen_US
dc.contributor.otherMassachusetts Institute of Technology. Biological Engineering Division.en_US
dc.date.accessioned2006-08-25T18:53:00Z
dc.date.available2006-08-25T18:53:00Z
dc.date.copyright2005en_US
dc.date.issued2005en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/33874
dc.descriptionThesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2005.en_US
dc.descriptionIncludes bibliographical references (leaves 40-43).en_US
dc.description.abstractAdult stem cells are potentially useful in many biomedical applications that can save lives and increase the quality of a patient's life, such as tissue engineering, cell replacement, and gene therapy. However, these applications are limited because of the difficulty in isolating and expanding pure populations of adult stem cells (ASCs). A major barrier to ASC expansion in vitro is their property of asymmetric cell kinetics. Our lab has developed a method, Suppression of Asymmetric Cell Kinetics (SACK), to expand ASCs in vitro by shifting their cell kinetics program from asymmetric to symmetric. We have found that guanine nucleotide precursors can be used to convert the kinetics of adult stem cells from asymmetric to symmetric, which promotes their exponential expansion. Previously, we have used the SACK method to derive hepatic and cholangiocyte stem cell strains from adult rat livers in vitro. These cell strains provide an assay to evaluate whether growth factors and cytokines previously implicated in proliferation of progenitor cells act by converting the kinetics of the stem cells in the population from asymmetric to symmetric, and thus identify new SACK agents. We are evaluating three agents, Wnt, IGF- 1, and Sonic hedgehog (Shh).en_US
dc.description.abstract(cont.) Wnt has been found to cause self-renewal and proliferation of hematopoietic stem cells (HSCs) in vitro. IGF- 1 also plays a role in hematopoietic progenitor self-renewal in vivo as well as in tissue maturation. Shh has been implicated in the proliferation of primitive neural cells as well as in cellular proliferation during invertebrate development. Thus far, we have found that Wnt peptide shifts the cell kinetics from asymmetric to symmetric and may reduce the generation time, whereas IGF-1 appears only to affect generation time. Studies involving Shh are currently underway. We are also currently investigating whether Wnt acts additively or synergistically with guanine nucleotide precursors to shift cell kinetic symmetry. Discovering new SACK agents will allow us to obtain purer populations of ASCs that can be used to study properties unique to stem cells. Furthermore, the observation that Wnt shifts the kinetics of adult rat hepatic stem cells from asymmetric to symmetric implicates the involvement of similar cell kinetics symmetry mechanisms in the proliferation effect of Wnt on murine and human HSCs.en_US
dc.description.statementofresponsibilityby Michal Ganz.en_US
dc.format.extent44 leavesen_US
dc.format.extent2296186 bytes
dc.format.extent2297923 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582
dc.subjectBiological Engineering Division.en_US
dc.titleInvestigation of growth factors and cytokines that suppress adult stem cell asymmetric cell kineticsen_US
dc.typeThesisen_US
dc.description.degreeS.M.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.identifier.oclc66464525en_US


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