Reprogramming of adult human fibroblasts into induced pluripotent stem (iPS) cells has generated significant excitement in the fields of regenerative medicine and stem cell biology. IPS cells avoid the ethical issues surrounding human embryonic stem (hES) cells, and also have the potential for being patient- and diseasespecific. However, at present the field is still in its infancy and significant concerns still exist over the efficiency, safety, and efficacy of iPS cell-based derivatives. This Stanford-Gladstone porposal on """"""""IPS Cells for the Understanding and Treatment of Heart Disease"""""""" will investigate the following aspects:
Specific Aim 1 : To generate iPS cells from adult human adipose stromal cells (hASCs) using non-viral minicircle plasmids.
Specific Aim 2 : To compare human adipose stromal cell-derived induced pluripotent stem (hASC-iPS) cells and hES cells using network pathway analyses.
Specific Aim 3 : To significantly enhance the yield of hASC-iPS cells by mlRNA reprogramming approach.
Specific Aim 4 : To assess the fate of IPS cell-derived cardiomyocytes (iPSC-CMs) in vivo using novel molecular imaging technology.
Specific Aim 5 : To demonstrate that transplantation of iPSC-CMs in an infarcted heart model will lead to beneficial improvements in cardiac contractility, perfusion, and viability. To tackle these questions, we have assembled a team of interdisciplinary investigators. This team has broad expertise in areas such as stem cell biology, genetics, microRNA, surgery, small &large animal models, immunology, molecular imaging, and bioinformatics. Importantly, this team already has a rich history of collaborations already. Thus, we are confident that significant advances can be made over the next 7 years that will translate into iPS cell-based clinical therapies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL099776-06
Application #
8656739
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Buxton, Denis B
Project Start
2009-09-30
Project End
2016-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Stanford University
Department
Surgery
Type
Schools of Medicine
DUNS #
City
Stanford
State
CA
Country
United States
Zip Code
94304
Zielins, Elizabeth R; Paik, Kevin; Ransom, Ryan C et al. (2016) Enrichment of Adipose-Derived Stromal Cells for BMPR1A Facilitates Enhanced Adipogenesis. Tissue Eng Part A 22:214-21
Ho, Yu-Sian; Tsai, Wan-Hsuan; Lin, Fen-Chiung et al. (2016) Cardioprotective Actions of TGFβRI Inhibition Through Stimulating Autocrine/Paracrine of Survivin and Inhibiting Wnt in Cardiac Progenitors. Stem Cells 34:445-55
Walmsley, Graham G; Senarath-Yapa, Kshemendra; Wearda, Taylor L et al. (2016) Surveillance of Stem Cell Fate and Function: A System for Assessing Cell Survival and Collagen Expression In Situ. Tissue Eng Part A 22:31-40
Chang, Andrew Y; Kittle, Jessie T; Wu, Sean M (2016) Regenerative Medicine: Potential Mechanisms of Cardiac Recovery in Takotsubo Cardiomyopathy. Curr Treat Options Cardiovasc Med 18:20
Tevlin, R; Walmsley, G G; Marecic, O et al. (2016) Stem and progenitor cells: advancing bone tissue engineering. Drug Deliv Transl Res 6:159-73
Sayed, Nazish; Liu, Chun; Wu, Joseph C (2016) Translation of Human-Induced Pluripotent Stem Cells: From Clinical Trial in a Dish to Precision Medicine. J Am Coll Cardiol 67:2161-76
Ogle, Brenda M; Bursac, Nenad; Domian, Ibrahim et al. (2016) Distilling complexity to advance cardiac tissue engineering. Sci Transl Med 8:342ps13
Burridge, Paul W; Diecke, Sebastian; Matsa, Elena et al. (2016) Modeling Cardiovascular Diseases with Patient-Specific Human Pluripotent Stem Cell-Derived Cardiomyocytes. Methods Mol Biol 1353:119-30
Agarwal, Shailesh; Loder, Shawn; Cholok, David et al. (2016) Local and Circulating Endothelial Cells Undergo Endothelial to Mesenchymal Transition (EndMT) in Response to Musculoskeletal Injury. Sci Rep 6:32514
Li, Guang; Xu, Adele; Sim, Sopheak et al. (2016) Transcriptomic Profiling Maps Anatomically Patterned Subpopulations among Single Embryonic Cardiac Cells. Dev Cell 39:491-507

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