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Comparison of Candidate Cell Populations for the Recellularization of Decellularized Heart Valves

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Abstract

Introduction

Heart valve tissue engineering may provide improved treatment for valvular heart disease, yet development of a tissue engineered heart valve (TEHV) has been limited by incomplete recellularization of the valve leaflets. In this study, we compare the leaflet recellularization potential of candidate cell populations.

Methods

Four cell populations were tested: bone marrow mononuclear cells (MNC), 5 million bone marrow mesenchymal stem cells (MSC), 10 million bone marrow mesenchymal stem cells (MSC2), and 5 million valve interstitial cells (VIC). Candidate cell populations were seeded onto decellularized heart valves and underwent similar conditioning in a low-flow bioreactor for 2 weeks.

Results

MSC2 valves demonstrated the best recellularization of the interstitial leaflet tissue as well as an appropriate cell phenotype, mechanical properties, and biochemical composition. MSC valves exhibited similar leaflet repopulation, yet had decreased mechanical and biochemical properties. MNC seeding resulted in minimal recellularization of the leaflet, though an additional time point group found cells present after 3 days, which seemed to disappear at 2 weeks. VIC seeding resulted in cell clumping on the leaflet surface and poor recellularization.

Conclusions

The results of this study suggest mesenchymal stem cells are a preferred cell population for TEHV recellularization. Additionally, MSCs demonstrate the ability for repopulation of the distal valve leaflet, which will lead to more complete recellularization of future TEHVs.

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Acknowledgments

AP acknowledges an investigator grant provided by the Institutional Development Award from the National Institute of General Medical Sciences of the NIH Award Number P20GM103638 and Umbilical Cord Matrix Project fund form the State of Kansas.

Conflict of interest

VeDepo M., Buse E., Paul A., Hopkins R., and Converse G. all declare that they have no conflicts of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Specifically, ovine aortic valves were harvested from juvenile sheep under approved IACUC protocols and in accordance with Guide for Care and Use of Laboratory Animals (National Institutes of Health Publication No. 85-23). This article does not contain any studies with human participants performed by any of the authors.

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Authors and Affiliations

  1. Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children’s Mercy Kansas City, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Mitchell VeDepo, Eric Buse, Richard Hopkins & Gabriel Converse

  2. Bioengineering Program, University of Kansas, 3135A Learned Hall, 1530 W. 15th St, Lawrence, KS, 66045, USA

    Mitchell VeDepo & Arghya Paul

  3. BioIntel Research Laboratory, Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, 66045, USA

    Arghya Paul

Authors
  1. Mitchell VeDepo
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  2. Eric Buse
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  3. Arghya Paul
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  4. Richard Hopkins
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  5. Gabriel Converse
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Corresponding author

Correspondence to Mitchell VeDepo.

Additional information

Associate Editor Michael R. King oversaw the review of this article.

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VeDepo, M., Buse, E., Paul, A. et al. Comparison of Candidate Cell Populations for the Recellularization of Decellularized Heart Valves. Cel. Mol. Bioeng. 11, 197–209 (2018). https://doi.org/10.1007/s12195-018-0524-0

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