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Commercialization of Pre-Clinical Cardiac Safety Using Stem Cell Derived Human Cardiomyocytes

Sethia, Vinay K.
http://rave.ohiolink.edu/etdc/view?acc_num=case1307731193

Abstract Details

2011, Master of Sciences, Case Western Reserve University, Biology.
This thesis provides a commercialization strategy for stem cell-derived human cardiomyocytes (SC-hCM) with an overview of pharmacological and electrophysiological profiles of SC-hCM and non-human Purkinje Fiber (PF) action potential (AP) assays. PF AP assays are commonly used to assess cardiac risk of pharmaceuticals in preclinical development but they often provide false negative or false positive results. The SC-hCM AP assay offers the potential advantages of increased pharmacological sensitivity, reduced compound consumption, higher throughput and cost effectiveness compared to conventional PF assays. The electrophysiological and pharmacological profiles of SC-hCMs were compared to canine and rabbit PFs. The effects of reference compounds were measured in ventricular-type SC-hCMs by perforated-patch, current clamp recording and compared with results obtained in PF AP assays. In conclusion, SC-hCMs provide an attractive alternative to PF AP assays; since this assay accurately predicts cardiac risk of known torsadogenic compounds and demonstrates an overall pharmacological sensitivity that is greater than conventional rabbit or canine PF assays
Roy Ritzmann, Ph.D (Committee Chair)
Christopher Cullis, Ph.D (Advisor)
Andrew Bruening-Wright, Ph.D (Committee Member)
Jean Welter, Ph.D (Committee Member)
59 p.
Biology; Entrepreneurship; Health Care; Health Care Management; Health Sciences; Marketing; Pharmaceuticals; Pharmacology; Physiology; Technology; Toxicology
Torsade de Pointes; Cardiomyocytes; human cardiomyocytes; Purkinje Fiber; Human embryonic stem cell; cardiac action potential; pre-clinical cardiac safety; Stem cell derived human cardiomyocytes; Drug

Recommended Citations

Citations

  • Sethia, V. K. (2011). Commercialization of Pre-Clinical Cardiac Safety Using Stem Cell Derived Human Cardiomyocytes [Master's thesis, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1307731193

    APA Style (7th edition)

  • Sethia, Vinay. Commercialization of Pre-Clinical Cardiac Safety Using Stem Cell Derived Human Cardiomyocytes. 2011. Case Western Reserve University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1307731193.

    MLA Style (8th edition)

  • Sethia, Vinay. "Commercialization of Pre-Clinical Cardiac Safety Using Stem Cell Derived Human Cardiomyocytes." Master's thesis, Case Western Reserve University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1307731193

    Chicago Manual of Style (17th edition)

case1307731193
575
© 2011, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.