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 #
5P01HL094374-04
Application #
8485644
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$279,901
Indirect Cost
$112,098
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Hofsteen, Peter; Robitaille, Aaron Mark; Strash, Nicholas et al. (2018) ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem Cells. iScience 2:88-100
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Palpant, Nathan J; Wang, Yuliang; Hadland, Brandon et al. (2017) Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis. Cell Rep 20:1597-1608
Palpant, Nathan J; Pabon, Lil; Friedman, Clayton E et al. (2017) Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nat Protoc 12:15-31
Yang, Xiulan; Murry, Charles E (2017) One Stride Forward: Maturation and Scalable Production of Engineered Human Myocardium. Circulation 135:1848-1850

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