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Alignment of inducible vascular progenitor cells on a micro-bundle scaffold improves cardiac repair following myocardial infarction

  • Anurag Jamaiyar
  • Weiguo Wan
  • Vahagn Ohanyan
  • Molly Enrick
  • Danielle Janota
  • Devan Cumpston
  • Hokyung Song
  • Kelly Stevanov
  • Christopher L. Kolz
  • Tatev Hakobyan
  • Feng Dong
  • Bi-min Zhang Newby
  • William M. Chilian
  • Liya YinEmail author
Original Contribution

Abstract

Ischemic heart disease is still the leading cause of death even with the advancement of pharmaceutical therapies and surgical procedures. Early vascularization in the ischemic heart is critical for a better outcome. Although stem cell therapy has great potential for cardiovascular regeneration, the ideal cell type and delivery method of cells have not been resolved. We tested a new approach of stem cell therapy by delivery of induced vascular progenitor cells (iVPCs) grown on polymer micro-bundle scaffolds in a rat model of myocardial infarction. iVPCs partially reprogrammed from vascular endothelial cells (ECs) had potent angiogenic potential and were able to simultaneously differentiate into vascular smooth muscle cells (SMCs) and ECs in 2D culture. Under hypoxic conditions, iVPCs also secreted angiogenic cytokines such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as measured by enzyme-linked immunosorbent assay (ELISA). A longitudinal micro-scaffold made from poly(lactic-co-glycolic acid) was sufficient for the growth and delivery of iVPCs. Co-cultured ECs and SMCs aligned well on the micro-bundle scaffold similarly as in the vessels. 3D cell/polymer micro-bundles formed by iVPCs and micro-scaffolds were transplanted into the ischemic myocardium in a rat model of myocardial infarction (MI) with ligation of the left anterior descending artery. Our in vivo data showed that iVPCs on the micro-bundle scaffold had higher survival, and better retention and engraftment in the myocardium than free iVPCs. iVPCs on the micro-bundles promoted better cardiomyocyte survival than free iVPCs. Moreover, iVPCs and iVPC/polymer micro-bundles treatment improved cardiac function (ejection fraction and fractional shortening, endocardial systolic volume) measured by echocardiography, increased vessel density, and decreased infarction size [endocardial and epicardial infarct (scar) length] better than untreated controls at 8 weeks after MI. We conclude that iVPCs grown on a polymer micro-bundle scaffold are new promising approach for cell-based therapy designed for cardiovascular regeneration in ischemic heart disease.

Keywords

Vascular progenitor cells Ischemic heart diseases Stem cells Myocardial infarction Cardiovascular regeneration Micro-bundle scaffold 

Notes

Acknowledgements

Our summer medical student Alisha Lall for cutting heart slides for the project. The research is funded by National Institutes of Health Grant RHL100828Z, R01 83366 (WMC), 1R01HL135110-01 (WMC,LY) and Collaborative Research and Development Projects from Austen BioInnovation Institute in Akron, OH, by Grants 14BGIA18770028 from American Heart Association and National Institutes of Health 1R15HL115540-01 (LY).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

All animal studies were performed using protocols approved by the Northeast Ohio Medical University Institutional Animal Care and Use Committee and comply with the ethical standards laid down in the 1964 Declaration of Helsinki and all later amendments. This manuscript does not contain clinical studies or patient data.

Supplementary material

395_2017_631_MOESM1_ESM.pdf (175 kb)
Supplementary material 1 (PDF 174 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Anurag Jamaiyar
    • 1
    • 2
  • Weiguo Wan
    • 1
  • Vahagn Ohanyan
    • 1
  • Molly Enrick
    • 1
  • Danielle Janota
    • 1
  • Devan Cumpston
    • 1
  • Hokyung Song
    • 3
  • Kelly Stevanov
    • 1
  • Christopher L. Kolz
    • 1
  • Tatev Hakobyan
    • 1
  • Feng Dong
    • 1
  • Bi-min Zhang Newby
    • 3
  • William M. Chilian
    • 1
  • Liya Yin
    • 1
    Email author
  1. 1.Department of Integrative Medical SciencesNortheast Ohio Medical UniversityRootstownUSA
  2. 2.School of Biomedical SciencesKent State UniversityKentUSA
  3. 3.Department of Chemical and Biomolecular EngineeringThe University of AkronAkronUSA

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