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Author Notes:

Michael E. Davis, PhD, Associate Professor of Biomedical Engineering and Medicine, Wallace H. Coulter Department of Biomedical Engineering at Emory University, and Georgia Institute of Technology, 1760 Haygood Drive, Suite E486, Atlanta, GA 30322, USA. michael.davis@bme.emory.edu, 404-727-9858 (o), 404-727-9873 (f).

Authors reported no conflicts of interest.

Subjects:

Research Funding:

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.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Progenitor cell
  • Hydrogel
  • Heart
  • Gene expression
  • Self assembling peptide
  • STEM-CELLS
  • HEART REGENERATION
  • SIGNALING PROMOTES
  • KAPPA-B
  • PDGF-BB
  • SURVIVAL
  • DELIVERY
  • PATHWAY
  • MATURATION
  • MIGRATION

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

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Journal Title:

Biomaterials

Volume:

Volume 35, Number 28

Publisher:

, Pages 8103-8112

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2014 Elsevier Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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