Building Cardiac Tissue from Stem Cells and Natural Matrices
Grant Award Details
Grant Type:
Grant Number:
RN2-00921
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$1,656,083
Status:
Closed
Progress Reports
Reporting Period:
Year 1
Reporting Period:
Year 2
Reporting Period:
Year 3
Reporting Period:
Year 4
Reporting Period:
Year 5
Grant Application Details
Application Title:
Building Cardiac Tissue from Stem Cells and Natural Matrices
Public Abstract:
Congestive heart failure afflicts 4.8 million people, with 400,000 new cases each year. Myocardial infarction (MI), also known as a "heart attack", leads to a loss of cardiac tissue and impairment of left ventricular function. Because the heart does not contain a significant number of multiplying stem, precursor, or reserve cells, it is unable to effectively heal itself after injury and the heart tissue eventually becomes scar tissue. The subsequent changes in the workload of the heart may, if the scar is large enough, deteriorate further leading to congestive heart failure. Many stem cell strategies are being explored for the regeneration of heart tissue, however; full cardiac tissue repair will only become possible when two critical areas of tissue regeneration are addressed: 1) the generation of a sustainable, purified source of functional cardiac progenitors and 2) employment of cell delivery methods leading to functional integration with host tissue. This proposal will explore both of these 2 critical areas towards the development of a living cardiac patch material that will enable the regeneration of scarred hearts.
Statement of Benefit to California:
The research proposed in expected to result in new techniques and methodology for the differentiation of stem cell-derived cardiomyocytes and delivery methods optimal for therapeutic repair of scarred heart tissue after a heart attack. The citizens of California could benefit from this research in three ways. The most significant impact would be in the potential potential for new medical therapies to treat a large medical problem. The second benefit is in the potential for these technologies to bring new usiness ventures to the state of California. The third benefit is the stem cell training of the students and postdocs involved in this study.
Publications
- J Stem Cells Regen Med (2012): Activin A and BMP4 Signaling for Efficient Cardiac Differentiation of H7 and H9 Human Embryonic Stem Cells. (PubMed: 24693198)
- J Biomed Mater Res B Appl Biomater (2012): Cardiac tissue development for delivery of embryonic stem cell-derived endothelial and cardiac cells in natural matrices. (PubMed: 22888031)
- Biores Open Access (2014): Combinatorial fibronectin and laminin signaling promote highly efficient cardiac differentiation of human embryonic stem cells. (PubMed: 25126479)
- J Biomed Mater Res A (2024): Comparing fabrication techniques for engineered cardiac tissue. (PubMed: 38752415)
- J Biol Eng (2013): Endothelial cells derived from embryonic stem cells respond to cues from topographical surface patterns. (PubMed: 23819656)
- Stem Cells Dev (2011): Endothelial cells from embryonic stem cells in a chemically defined medium. (PubMed: 21446878)
- J Vasc Res (2011): Functional characterization of embryonic stem cell-derived endothelial cells. (PubMed: 21625175)
- Cell Commun Signal (2017): Metabolic shift in density-dependent stem cell differentiation. (PubMed: 29052507)
- Tissue Eng Part C Methods (2011): Multi-scale Biomimetic Topography for the Alignment of Neonatal and Embryonic Stem Cell-derived Heart Cells. (PubMed: 21235325)
- PLoS One (2016): Multifactorial Optimizations for Directing Endothelial Fate from Stem Cells. (PubMed: 27907001)
- J Vis Exp (2012): Rapid fibroblast removal from high density human embryonic stem cell cultures. (PubMed: 23128236)
- Adv Mater (2011): Shrink-Film Configurable Multiscale Wrinkles for Functional Alignment of Human Embryonic Stem Cells and their Cardiac Derivatives. (PubMed: 22065428)
- Stem Cells Cloning (2014): Specialized mouse embryonic stem cells for studying vascular development. (PubMed: 25328412)
- Stem Cells Dev (2013): Specialized tip/stalk-like and phalanx-like endothelial cells from embryonic stem cells. (PubMed: 23249281)
- Stem Cell Rev (2012): Stage-Specific Cardiomyocyte Differentiation Method for H7 and H9 Human Embryonic Stem Cells. (PubMed: 22890895)
- J Vis Exp (2014): Tissue engineering: construction of a multicellular 3D scaffold for the delivery of layered cell sheets. (PubMed: 25350752)