TY - JOUR
T1 - Genetic and Tissue Engineering Approaches to Modeling the Mechanics of Human Heart Failure for Drug Discovery
AU - Greenberg, Michael J.
AU - Daily, Neil J.
AU - Wang, Ann
AU - Conway, Michael K.
AU - Wakatsuki, Tetsuro
N1 - Funding Information:
The authors acknowledge funding support partly from the National Institutes of Health (R01HL141086, R00HL123623 to MG, and R43GM109735, R43AG054270, R01HL109505 to TW) and the March of Dimes Foundation (FY18-BOC-430198 to MG).
Publisher Copyright:
© Copyright © 2018 Greenberg, Daily, Wang, Conway and Wakatsuki.
PY - 2018/9/19
Y1 - 2018/9/19
N2 - Heart failure is the leading cause of death in the western world and as such, there is a great need for new therapies. Heart failure has a variable presentation in patients and a complex etiology; however, it is fundamentally a condition that affects the mechanics of cardiac contraction, preventing the heart from generating sufficient cardiac output under normal operating pressures. One of the major issues hindering the development of new therapies has been difficulties in developing appropriate in vitro model systems of human heart failure that recapitulate the essential changes in cardiac mechanics seen in the disease. Recent advances in stem cell technologies, genetic engineering, and tissue engineering have the potential to revolutionize our ability to model and study heart failure in vitro. Here, we review how these technologies are being applied to develop personalized models of heart failure and discover novel therapeutics.
AB - Heart failure is the leading cause of death in the western world and as such, there is a great need for new therapies. Heart failure has a variable presentation in patients and a complex etiology; however, it is fundamentally a condition that affects the mechanics of cardiac contraction, preventing the heart from generating sufficient cardiac output under normal operating pressures. One of the major issues hindering the development of new therapies has been difficulties in developing appropriate in vitro model systems of human heart failure that recapitulate the essential changes in cardiac mechanics seen in the disease. Recent advances in stem cell technologies, genetic engineering, and tissue engineering have the potential to revolutionize our ability to model and study heart failure in vitro. Here, we review how these technologies are being applied to develop personalized models of heart failure and discover novel therapeutics.
KW - drug discovery
KW - gene editing
KW - heart failure
KW - high-throughput screening
KW - human induced pluripotent stem cells
KW - length-tension relationship
KW - rare heart disease
KW - tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=85061353736&partnerID=8YFLogxK
U2 - 10.3389/fcvm.2018.00120
DO - 10.3389/fcvm.2018.00120
M3 - Review article
C2 - 30283789
AN - SCOPUS:85061353736
SN - 2297-055X
VL - 5
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 120
ER -