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A Highly Conductive 3D Cardiac Patch Fabricated Using Cardiac Myocytes Reprogrammed from Human Adipogenic Mesenchymal Stem Cells

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Abstract

Purpose

The objective of this study was to bioengineer 3D patches from cardiac myocytes that have been reprogrammed from human adipogenic mesenchymal stem cells (hADMSCs).

Methods

Human adipogenic mesenchymal stem cells (hADMSCs) were reprogrammed to form cardiac myocytes using transcription factors ETS2 and MESP1. Reprogrammed cardiac myocytes were cultured in a fibrin gel to bioengineer 3D patch patches. The effect of initial plating density (1–25 million cells per patch), time (28-day culture period) and treatment with 1 μM isoproterenol and 1 μM epinephrine were evaluated.

Results

3D patches were fabricated using cardiac myocytes that have been reprogrammed from hADMSCs. Based on optimization studies, it was determined that 10 million cells were needed to bioengineer a single patch, that measured 2 × 2 cm2. Furthermore, 3D patches fabricated 10 million cells were stable in culture for up to 28 days. Treatment of 3D patches with 1 μM isoproterenol and 1 μM epinephrine resulted in an increase in the electrical properties, as measured by electrical impulse amplitude and frequency. An increase in the expression of mTOR, KCNV1, GJA5, KCNJ16, CTNNT2, KCNV2, MYO3, FOXO1 and KCND2 was noted in response to treatment of 3D patches with isoproterenol and epinephrine.

Conclusion

Based on the results of this study, there is evidence to support the successful fabrication of a highly functional 3D patches with measurable electrical activity using cardiac myocytes reprogrammed from hADMSCs. 3D patches fabricated using optimal conductions described in this study can be used to improve the functional properties of failing hearts. Predominantly, in case of the infarcted hearts with partial loss of electrical activity, the electrical properties of the 3D patches may restore the electrical activity of the heart.

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Authors and Affiliations

  1. Stem Cell Engineering, Texas Heart Institute, 6770 Bertner Avenue, Houston, TX, 77225-0345, USA

    Reza Abbasgholizadeh, Jose Francisco Islas, Vladimir N. Potaman, Robert J. Schwartz & Ravi K. Birla

  2. Synthecon, Inc., 8977 Interchange Drive, Houston, Texas, 77054, USA

    Stephen Navran

  3. Department of Biology and Biochemistry, Science and Engineering Research Center (SERC-Building 445), 3605 Cullen Blvd, Room 5004, Houston, TX, 77204-5060, USA

    Robert J. Schwartz

Authors
  1. Reza Abbasgholizadeh
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  2. Jose Francisco Islas
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  3. Stephen Navran
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  4. Vladimir N. Potaman
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  5. Robert J. Schwartz
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  6. Ravi K. Birla
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Corresponding author

Correspondence to Ravi K. Birla.

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Associate Editor Ajit Yoganathan oversaw the review of this article

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Abbasgholizadeh, R., Islas, J.F., Navran, S. et al. A Highly Conductive 3D Cardiac Patch Fabricated Using Cardiac Myocytes Reprogrammed from Human Adipogenic Mesenchymal Stem Cells. Cardiovasc Eng Tech 11, 205–218 (2020). https://doi.org/10.1007/s13239-019-00451-0

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  • DOI: https://doi.org/10.1007/s13239-019-00451-0

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