DOI: 10.1073/pnas.0711507105. Cardiogenic small molecules that enhance myocardial repair by stem cells

Cardiogenic small molecules that enhance myocardial repair by stem cells

10.1073/pnas.0711507105

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The clinical success of stem cell therapy for myocardial repair hinges on a better understanding of cardiac fate mechanisms. We have identified small molecules involved in cardiac fate by screening a chemical library for activators of the signature gene Nkx2.5 , using a luciferase knockin bacterial artificial chromosome (BAC) in mouse P19CL6 pluripotent stem cells. We describe a family of sulfonyl-hydrazone (Shz) small molecules that can trigger cardiac mRNA and protein expression in a variety of embryonic and adult stem/progenitor cells, including human mobilized peripheral blood mononuclear cells (M-PBMCs). Small-molecule-enhanced M-PBMCs engrafted into the rat heart in proximity to an experimental injury improved cardiac function better than control cells. Recovery of cardiac function correlated with persistence of viable human cells, expressing human-specific cardiac mRNAs and proteins. Shz small molecules are promising starting points for drugs to promote myocardial repair/regeneration by activating cardiac differentiation in M-PBMCs.

Bibliography

Sadek, H., Hannack, B., Choe, E., Wang, J., Latif, S., Garry, M. G., Garry, D. J., Longgood, J., Frantz, D. E., Olson, E. N., Hsieh, J., & Schneider, J. W. (2008). Cardiogenic small molecules that enhance myocardial repair by stem cells. Proceedings of the National Academy of Sciences, 105(16), 6063â6068.

Authors 12

Hesham Sadek (first)
Britta Hannack (additional)
Elizabeth Choe (additional)
Jessica Wang (additional)
Shuaib Latif (additional)
Mary G. Garry (additional)
Daniel J. Garry (additional)
Jamie Longgood (additional)
Doug E. Frantz (additional)
Eric N. Olson (additional)
Jenny Hsieh (additional)
Jay W. Schneider (additional)

References 19 Referenced 105

Dates

Type	When
Created	17 years, 4 months ago (April 17, 2008, 8:56 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:01 p.m.)
Indexed	4 months, 2 weeks ago (April 11, 2025, 4:11 a.m.)
Issued	17 years, 4 months ago (April 22, 2008)
Published	17 years, 4 months ago (April 22, 2008)
Published Online	17 years, 4 months ago (April 22, 2008)
Published Print	17 years, 4 months ago (April 22, 2008)

Funders 0

None

BibTeX

@article{Sadek_2008, title={Cardiogenic small molecules that enhance myocardial repair by stem cells}, volume={105}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0711507105}, DOI={10.1073/pnas.0711507105}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sadek, Hesham and Hannack, Britta and Choe, Elizabeth and Wang, Jessica and Latif, Shuaib and Garry, Mary G. and Garry, Daniel J. and Longgood, Jamie and Frantz, Doug E. and Olson, Eric N. and Hsieh, Jenny and Schneider, Jay W.}, year={2008}, month=apr, pages={6063–6068} }

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