Cardiogenic small molecules that enhance myocardial repair by stem cells

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

Research output: Contribution to journalArticle

102 Citations (Scopus)

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 sulfonylhydrazone (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.

Original languageEnglish (US)
Pages (from-to)6063-6068
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number16
DOIs
StatePublished - Apr 22 2008

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Blood Cells
Stem Cells
Small Molecule Libraries
Bacterial Artificial Chromosomes
Pluripotent Stem Cells
Messenger RNA
Adult Stem Cells
Recovery of Function
Cell- and Tissue-Based Therapy
Luciferases
Regeneration
Proteins
Wounds and Injuries
Pharmaceutical Preparations
Genes

Keywords

  • Cardiogenesis
  • Chemical biology
  • High-throughput screen
  • Myocardial repair

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Cardiogenic small molecules that enhance myocardial repair by stem cells. / Sadek, Hesham A; Hannack, Britta; Choe, Elizabeth; Wang, Jessica; Latif, Shuaib; Garry, Mary G.; Garry, Daniel J.; Longgood, Jamie; Frantz, Doug E.; Olson, Eric N; Hsieh, Jenny; Schneider, Jay W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 16, 22.04.2008, p. 6063-6068.

Research output: Contribution to journalArticle

Sadek, HA, Hannack, B, Choe, E, Wang, J, Latif, S, Garry, MG, Garry, DJ, Longgood, J, Frantz, DE, Olson, EN, Hsieh, J & Schneider, JW 2008, 'Cardiogenic small molecules that enhance myocardial repair by stem cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 16, pp. 6063-6068. https://doi.org/10.1073/pnas.0711507105
Sadek, Hesham A ; Hannack, Britta ; Choe, Elizabeth ; Wang, Jessica ; Latif, Shuaib ; Garry, Mary G. ; Garry, Daniel J. ; Longgood, Jamie ; Frantz, Doug E. ; Olson, Eric N ; Hsieh, Jenny ; Schneider, Jay W. / Cardiogenic small molecules that enhance myocardial repair by stem cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 16. pp. 6063-6068.
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