Core A: While pluripotent stem cells and their differentiated progeny have tremendous promise for cardiac repair, their routine culture is demanding and requires considerable expertise and continuous attention to quality control. Based on our extensive prior experience with these cells, we have found that centralization of cell culture efforts is the best way to ensure consistency and efficiency in the large-scale production of undifferentiated and differentiated cells. Hence, the primary goal ofthe Stem Cell Core will be to generate large numbers of undifferentiated embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and cardiac derivatives for distribution to the individual projects in this program. The Core will also work closely with investigators in Project 2 to optimize the derivation of cardiomyocytes from canine ESCs. Finally, the Core will also develop and share optimized protocols for the genetic modification of ESCs and iPSCs, including the generation of cell type specific reporter lines via transgenesis in bacterial artficial chromosomes (BACs). In sum, the Core will undertake three specific aims: 1) to provide the individual projects with the stem cells and cardiac derivatives needed to complete their respective aims, 2) to develop BAC transgenesis and optimize the delivery of modified BACs into human ESCs and iPSCs), and 3) to provide training and technical assistance with in vitro experiments involving pluripotent stem cells or their differentiated progeny.

Public Health Relevance

The goal of this program is to develop stem cell based therapies for myocardial infarction, the number one cause of death in the U.S. However, the culture of stem cells is technically challenging, and so we need a centralized Stem Cell Core for the scaled production of stem cells and stem cell-derived heart muscle cells.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL094374-05
Application #
8676870
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
$646,531
Indirect Cost
$251,493
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hofsteen, Peter; Robitaille, Aaron M; Chapman, Daniel Patrick et al. (2016) Quantitative proteomics identify DAB2 as a cardiac developmental regulator that inhibits WNT/β-catenin signaling. Proc Natl Acad Sci U S A 113:1002-7
Ruan, Jia-Ling; Tulloch, Nathaniel L; Razumova, Maria V et al. (2016) Mechanical Stress Conditioning and Electrical Stimulation Promote Contractility and Force Maturation of Induced Pluripotent Stem Cell-Derived Human Cardiac Tissue. Circulation 134:1557-1567
Qin, Wan; Roberts, Meredith A; Qi, Xiaoli et al. (2016) Depth-resolved 3D visualization of coronary microvasculature with optical microangiography. Phys Med Biol 61:7536-7550
Pioner, Josè Manuel; Racca, Alice W; Klaiman, Jordan M et al. (2016) Isolation and Mechanical Measurements of Myofibrils from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Stem Cell Reports 6:885-96
Kolwicz Jr, Stephen C; Odom, Guy L; Nowakowski, Sarah G et al. (2016) AAV6-mediated Cardiac-specific Overexpression of Ribonucleotide Reductase Enhances Myocardial Contractility. Mol Ther 24:240-50
Hartman, Matthew E; Dai, Dao-Fu; Laflamme, Michael A (2016) Human pluripotent stem cells: Prospects and challenges as a source of cardiomyocytes for in vitro modeling and cell-based cardiac repair. Adv Drug Deliv Rev 96:3-17
Carson, Daniel; Hnilova, Marketa; Yang, Xiulan et al. (2016) Nanotopography-Induced Structural Anisotropy and Sarcomere Development in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells. ACS Appl Mater Interfaces 8:21923-32
Thies, R Scott; Murry, Charles E (2015) The advancement of human pluripotent stem cell-derived therapies into the clinic. Development 142:3077-84
Palpant, Nathan J; Hofsteen, Peter; Pabon, Lil et al. (2015) Cardiac development in zebrafish and human embryonic stem cells is inhibited by exposure to tobacco cigarettes and e-cigarettes. PLoS One 10:e0126259
Ruan, Jia-Ling; Tulloch, Nathaniel L; Saiget, Mark et al. (2015) Mechanical Stress Promotes Maturation of Human Myocardium From Pluripotent Stem Cell-Derived Progenitors. Stem Cells 33:2148-57

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