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Development of Pluripotent Amniotic Stem Cell Banks for Disease Modeling

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43GM097768-01
Agency Tracking Number: R43GM097768
Amount: $149,305.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIGMS
Solicitation Number: PA10-050
Timeline
Solicitation Year: 2011
Award Year: 2011
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
440 BURROUGHS ST
DETROIT, MI 48202-3429
United States
DUNS: 829227540
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 JAMES ELIASON
 (313) 483-0385
 jeliason@gmail.com
Business Contact
 JAMES ELIASON
Phone: (313) 405-7705
Email: aa3374@wayne.edu
Research Institution
 Stub
Abstract

DESCRIPTION (provided by applicant): Direct reprogramming of somatic cells with the transcription factors Oct4 (also called Pou5f1), Sox2, Klf4 and Myc1 yields induced Pluripotent Stem (iPS) cells with marked similarity to Embryonic Stem (ES) cells. When the source of the cells is patients affected by various disorders iPS cells promise to be excellent models to study the gradual pathogenesis of disease. However, there is recent evidence that iPS cells derived from adult tissues retain residual DNA methylation signatures characteristic of their somatic tissue of origin, which appears to restrict their differentiation potential. Human amniotic fluid (AF) cells have been used for prenatal diagnosis of chromosomal and Mendelian disorders for decades. Thereis a subpopulation of cells in AF that expresses the tyrosine kinase receptor c-Kit appear to have stem cell-like properties. Developmentally and functionally, they represent a class of stem cells with intermediate characteristics between embryonic and adult stem cells. Our hypotheses are that c-kit expressing AF cells can be reprogrammed using fewer exogenous proteins than necessary with adult cells and that the resulting iPS cells will have methylation patterns more similar to embryonic stem cells than toadult derived iPS cells. Such pluripotent stem cell lines would provide models with which to investigate the underlying mechanisms of a variety of genetic diseases, leading to new diagnostic and treatment modalities. Human amniotic fluid may provide a source of cells capable of generating more applicable disease-specific iPS cells. Our specific aims are: 1) characterize subpopulations of cells obtained from AF after cytogenetic diagnosis has confirmed the presence of genetic abnormalities; 2) determine minimal requirements for reprogramming AF cell subpopulations identified in Aim 1 to generate iPS cells. Our long-term goal is to develop banks of AF derived iPS cell lines representing different genetically related diseases. PUBLIC HEALTH RELEVANCE:We propose to create stem cell lines for the study of genetic diseases from amniotic fluid cells left over after diagnosis. Such stem cell lines would provide excellent models with which to investigate the underlying mechanisms of a variety of geneticdiseases, leading to new diagnostic and treatment modalities.

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

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