The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1 activation

Archana V. Boopathy, Pao Lin Che, Inthirai Somasuntharam, Vincent F. Fiore, E. Bernadette Cabigas, Kiwon Ban, Milton E. Brown, Yoshie Narui, Thomas H. Barker, Young Sup Yoon, Khalid Salaita, Andrés J. García, Michael E. Davis

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Myocardial infarction is the leading cause of death worldwide and phase I clinical trials utilizing cardiac progenitor cells (CPCs) have shown promising outcomes. Notch1 signaling plays a critical role in cardiac development and in the survival, cardiogenic lineage commitment, and differentiation of cardiac stem/progenitor cells. In this study, we functionalized self-assembling peptide (SAP) hydrogels with a peptide mimic of the Notch1 ligand Jagged1 (RJ) to evaluate the therapeutic benefit of CPC delivery in the hydrogels in a rat model of myocardial infarction. The behavior of CPCs cultured in the 3D hydrogels in vitro including gene expression, proliferation, and growth factor production was evaluated. Interestingly, we observed Notch1 activation to be dependent on hydrogel polymer density/stiffness with synergistic increase in presence of RJ. Our results show that RJ mediated Notch1 activation depending on hydrogel concentration differentially regulated cardiogenic gene expression, proliferation, and growth factor production in CPCs in vitro. In rats subjected to experimental myocardial infarction, improvement in acute retention and cardiac function was observed following cell therapy in RJ hydrogels compared to unmodified or scrambled peptide containing hydrogels. This study demonstrates the potential therapeutic benefit of functionalizing SAP hydrogels with RJ for CPC based cardiac repair.

Original languageEnglish
Pages (from-to)8103-8112
Number of pages10
JournalBiomaterials
Volume35
Issue number28
DOIs
Publication statusPublished - 2014 Sep

Bibliographical note

Funding Information:
This publication has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute , National Institutes of Health, Department of Health and Human Services , under Contract No. HHSN268201000043C to MED. This work was also supported by funding from the National Institutes of Health grant DP3DK094346 to YY and an American Heart Association Predoctoral fellowship 11PRE7840078 to AVB. KS is grateful for support from the NIH through R01-GM097399 .

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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