BRIGE: Engineering a BioMatrix Library Derived from Induced Pluripotent Stem Cells

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Technical Description:Human Induced Pluripotent Stem Cells (hiPSC) are adult cells (for example, skin cells derived from a biopsy) that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. They have great potential for drug screening, disease modeling, and eventually cell therapy for humans. Induced pluripotent stem cells (iPSCs) have great potential to understand diseases and develop therapeutics. Current matrices that are used for iPSC self-renewal and differentiation fail to recapitulate the complex signaling network during lineage specification. To address this issue, a novel Biomatrix Library will be generated in the proposed research to study the complex signaling during stem cell development. The unique feature of the proposed Biomatrix Library is the maintenance of the broad signaling capacity and preservation of signaling network during tissue development and morphogenesis. The specific tasks in the proposed study include: 1) generation and high-content characterization of a Biomatrix Library with various biochemical and biological properties; 2) high-throughput screening and validation of the Biomatrix Library for self-renewal and neural differentiation of iPSCs. The Biomatrix-based functional neural differentiation will be translated into a bioreactor to confirm the predicative effect from the screening. The long-term objective of this research is to obtain comprehensive understanding of cell-biomatrix interactions in regulating lineage-specific differentiation of iPSCs.Broader Significance and Importance:Induced pluripotent stem cells that are artificially derived from adult cells (e.g., skin cells) provide an alternative to embryonic stem cells for research. This 2012 Nobel Prize winning discovery represents an important advance in scientific research as they allow researchers to obtain pluripotent stem cells, which have the ability to become any cell type in the body, without the controversial use of embryos. Using well-established iPSC cell lines, the proposed study will identify the key interactions of cells, matrices and growth factors that could regulate cell fate decision. The research outcome will guide the biomimetic material design and the large scale generation of functional tissue cells for drug screening, disease modeling, and eventually cell therapy. This proposal details a transformative research plan to achieve highly efficient differentiation of iPSCs, regulated by the engineered Biomatrix that will be identified through innovative high content characterization, high-throughput screening, and functional analysis. The gained knowledge can be directly transformed to technology commercialization in the biopharmaceutical and biotechnology industries. Broadening Participation of Underrepresented Groups in EngineeringThe target populations of broadening participation activities in the proposed efforts include the African-American, Hispanic, and women students in Florida A&M University, a historically black college, Florida State University, a major research university with a large female enrollment, and Tallahassee community. Globally, the PI will provide mentoring and leadership training for Turkish women students using Global Educational Outreach in Science, Engineering and Technology portal. The PI will incorporate the skills required in industry such as current Good Manufacturing Practices and Quality by Design in the curriculum. These activities will bridge the gap between education and application, and also attract the students from under-represented groups to stay in science and engineering. The results from the proposed research and education efforts will be disseminated to K-12 students in Leon County School District and in Challenger Learning Center, to undergraduates in Biomedical Engineering Society, and to students in National Society of Black Engineers. In particular, the mentoring activities will broaden the participation of women in science and engineering locally and globally, especially in Tallahassee and Turkey.This research has been funded through the Broadening Participation Research Initiation Grants in Engineering solicitation, which is part of the Broadening Participation in Engineering Program of the Engineering Education and Centers Division.