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; Brett, Elizabeth A; Blackshear, Charles P et al. (2017) Purified Adipose-Derived Stromal Cells Provide Superior Fat Graft Retention Compared with Unenriched Stromal Vascular Fraction. Plast Reconstr Surg 139:911-914
Blackshear, Charles P; Flacco, John S; Vistnes, Stephanie M et al. (2017) Cell-Based Soft Tissue Reconstruction in a Hydrogel Scaffold. Ann Plast Surg 79:618-622
Brett, Elizabeth; Zielins, Elizabeth R; Chin, Monica et al. (2017) Isolation of CD248-expressing stromal vascular fraction for targeted improvement of wound healing. Wound Repair Regen 25:414-422
Agarwal, Shailesh; Loder, Shawn J; Breuler, Christopher et al. (2017) Strategic Targeting of Multiple BMP Receptors Prevents Trauma-Induced Heterotopic Ossification. Mol Ther 25:1974-1987
Galdos, Francisco X; Guo, Yuxuan; Paige, Sharon L et al. (2017) Cardiac Regeneration: Lessons From Development. Circ Res 120:941-959
Karra, Ravi; Walter, Agoston O; Wu, Sean M (2017) The relationship between cardiac endothelium and fibroblasts: it's complicated. J Clin Invest 127:2892-2894
Tevlin, Ruth; Seo, Eun Young; Marecic, Owen et al. (2017) Pharmacological rescue of diabetic skeletal stem cell niches. Sci Transl Med 9:
Blackshear, Charles Philip; Rector, Michael Anthony; Chung, Natalie Narie et al. (2017) Three-Dimensional Ultrasound Versus Computerized Tomography in Fat Graft Volumetric Analysis. Ann Plast Surg :
Serpooshan, Vahid; Liu, Yuan-Hung; Buikema, Jan W et al. (2017) Nkx2.5+?Cardiomyoblasts Contribute to Cardiomyogenesis in the Neonatal Heart. Sci Rep 7:12590
Sharma, Arun; Burridge, Paul W; McKeithan, Wesley L et al. (2017) High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Sci Transl Med 9:

Showing the most recent 10 out of 143 publications