hiPS Derived Assay for Screening Hematopoietic Differentiation Toxicant Effects

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43ES023490-01
Agency Tracking Number: R43ES023490
Amount: $210,823.00
Phase: Phase I
Program: SBIR
Awards Year: 2013
Solicitation Year: 2013
Solicitation Topic Code: NIEHS
Solicitation Number: ES13-003
Small Business Information
DUNS: 782932177
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (608) 628-5189
Business Contact
Phone: (608) 441-8332
Email: chuck.oehler@primorigen.com
Research Institution
Primorigen Biosciences (R) Abstract Primorigen Biosciences will use SBIR funds to develop a high-throughput toxicology assay system utilizing human ventricular cardiomyocytes (vCMs) differentiated from human induced pluripotent stem cells (hiPSCs). Phase Istudies will convert the small-molecule based, cytokine-free CardioTotal differentiation technology into a 96-well based high-throughput format. Automated flow cytometry will be used to monitor mesoderm specification by staining for brachyury, and to monitor differentiation efficiency and yield by staining for cardiac Troponin T and cardiac Troponin I. Cell viability and yield will be determined by cytoxicity assay, and contractility measurements will be performed by video microscopy and automated image analysis. Using these assays, a library of 20 toxicants selected from the Tox21 library will be screened, first for effects upon differentiation following early exposure, and second for toxicity and contractility effects by late exposure of differentiated cardiomyocytes. In Phase II, the system will be scaled up for 384-well format, and screening will be applied to a larger portion of the Tox21 library. Additional pluripotent cell lines will be tested to establish robustness, and secondary screenings will beinitiated to identify mechanisms of action. In Phase III, the system will be commercialized as an optimized, high-throughput cardiotoxicity screening system, provided as a service by Primorigen or customized for end-user internalization (for example at NIEHS NTP or EPA's ToxCast program). PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Current methods for toxicology screening rely on animal models or transformed human cell lines, neither of which can recapitulate fully the developmental processes and mature cell phenotypes of human tissues. Human induced pluripotent stem cell-derived cardiomyocytes offer a unique cell source for examining the effects of toxicants upon differentiation processes and upon the mature cardiomyocyte cell type. Primorigen Biosciences will develop a high throughput cardiomyocyte-based screening assay that will enable screening of the Tox21 library of compounds.

* Information listed above is at the time of submission. *

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