Abstract
Myocardial fibrosis is a hallmark of cardiac remodeling, which can progressively lead to heart failure, a leading cause of death worldwide. The effector cells of fibrosis in the heart are cardiac fibroblasts (CFs). There is currently no effective therapeutic strategy clinically available to specifically attenuate maladaptive responses of CFs. Large-scale applications such as high-throughput drug screening are difficult due to the limited availability of human primary CFs, thus limiting the development of future treatments. Here, we describe a robust induction protocol that can be used to generate a scalable, consistent, genetically defined source of quiescent CFs from human induced pluripotent stem cells for cardiac fibrosis modeling, drug discovery, and tissue engineering.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Hinderer S, Schenke-Layland K (2019) Cardiac fibrosis – a short review of causes and therapeutic strategies. Adv Drug Deliv Rev 146:77–82
Zeisberg M, Kalluri R (2013) Cellular mechanisms of tissue fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis. Am J Physiol Cell Physiol 304(3):C216–C225
Furtado MB, Costa MW, Pranoto EA, Salimova E, Pinto AR, Lam NT, Park A, Snider P, Chandran A, Harvey RP, Boyd R, Conway SJ, Pearson J, Kaye DM, Rosenthal NA (2014) Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair. Circ Res 114(9):1422–1434
Shi Y, Inoue H, Wu JC, Yamanaka S (2017) Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16(2):115–130
Zhang H, Tian L, Shen M, Tu C, Wu H, Gu M, Paik DT, Wu JC (2019) Generation of quiescent cardiac fibroblasts from human induced pluripotent stem cells for in vitro modeling of cardiac fibrosis. Circ Res 125(5):552–566
Tabula Muris Consortium, Overall coordination, Logistical coordination, Organ collection and processing, Library preparation and sequencing, Computational data analysis, Cell type annotation, Writing group, Supplemental text writing group, Principal investigators (2018) Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 562(7727):367–372
Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, Lan F, Diecke S, Huber B, Mordwinkin NM, Plews JR, Abilez OJ, Cui B, Gold JD, Wu JC (2014) Chemically defined generation of human cardiomyocytes. Nat Methods 11(8):855–860
Bao X, Lian X, Hacker TA, Schmuck EG, Qian T, Bhute VJ, Han T, Shi M, Drowley L, Plowright A, Wang QD, Goumans MJ, Palecek SP (2016) Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nat Biomed Eng 1:0003
Swaney JS, Roth DM, Olson ER, Naugle JE, Meszaros JG, Insel PA (2005) Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase. Proc Natl Acad Sci U S A 102(2):437–442
Acknowledgments
This work was supported by research grants from: NIH R01 HL113006, R01 HL123968, R01 HL141371, R01 HL141851, and AHA 17MERIT33610009 (JCW).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Science+Business Media New York
About this protocol
Cite this protocol
Zhang, H., Shen, M., Wu, J.C. (2020). Generation of Quiescent Cardiac Fibroblasts Derived from Human Induced Pluripotent Stem Cells. In: Nagy, A., Turksen, K. (eds) Induced Pluripotent Stem (iPS) Cells. Methods in Molecular Biology, vol 2454. Humana, New York, NY. https://doi.org/10.1007/7651_2020_300
Download citation
DOI: https://doi.org/10.1007/7651_2020_300
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2118-9
Online ISBN: 978-1-0716-2119-6
eBook Packages: Springer Protocols