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Ellis BW, Traktuev DO, Merfeld-Clauss S, et al. Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure. Stem Cells. 2020;39(2):170-182doi: 10.1002/stem.3296.
Ellis, B. W., Traktuev, D. O., Merfeld-Clauss, S., Can, U. I., Wang, M., Bergeron, R., Zorlutuna, P., & March, K. L. (2021). Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure. Stem cells (Dayton, Ohio), 39(2), 170-182. https://doi.org/10.1002/stem.3296
Ellis, Bradley W, et al. "Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure." Stem cells (Dayton, Ohio) vol. 39,2 (2021): 170-182. doi: https://doi.org/10.1002/stem.3296
Ellis BW, Traktuev DO, Merfeld-Clauss S, Can UI, Wang M, Bergeron R, Zorlutuna P, March KL. Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure. Stem Cells. 2021 Feb;39(2):170-182. doi: 10.1002/stem.3296. Epub 2020 Dec 23. PMID: 33159685; PMCID: PMC7855817.
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Stem Cells. 2021 Feb;39(2):170-182. doi: 10.1002/stem.3296. Epub 2020 Dec 23.

Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure.

Stem cells (Dayton, Ohio)

Bradley W Ellis, Dmitry O Traktuev, Stephanie Merfeld-Clauss, Uryan Isik Can, Meijing Wang, Ray Bergeron, Pinar Zorlutuna, Keith L March

Affiliations

  1. Bioengineering Graduate Program, University of Notre Dame, Notre Dame, Indiana, USA.
  2. Division of Cardiovascular Medicine and Center for Regenerative Medicine, University of Florida, Gainesville, Florida, USA.
  3. Malcom Randall Veterans' Affairs Medical Center, Gainesville, Florida, USA.
  4. Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana, USA.
  5. The Division of Cardiothoracic Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.

PMID: 33159685 PMCID: PMC7855817 DOI: 10.1002/stem.3296

Abstract

Heart transplantation is a life-saving therapy for end-stage organ failure. Organ deterioration during transportation limits storage to 4 hours, limiting hearts available. Approaches ameliorating organ damage could increase the number of hearts acceptable for transplantation. Prior studies show that adipose-derived stem/stromal cell secretome (ASC-S) rescues tissues from postischemic damage in vivo. This study tested whether ASC-S preserved the function of mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes (iCM) exposed to organ transportation and transplantation conditions. Hearts were subjected to cold University of Wisconsin (UW) cardioplegic solution ± ASC-S for 6 hours followed by analysis using the Langendorff technique. In parallel, the effects of ASC-S on the recovery of iCM from UW solution were examined when provided either during or after cold cardioplegia. Exposure of hearts and iCM to UW deteriorated contractile activity and caused cell apoptosis, worsening in iCM as a function of exposure time; these were ameliorated by augmenting with ASC-S. Silencing of superoxide dismutase 3 and catalase expression prior to secretome generation compromised the ASC-S cardiomyocyte-protective effects. In this study, a novel in vitro iCM model was developed to complement a rodent heart model in assessing efficacy of approaches to improve cardiac preservation. ASC-S displays strong cardioprotective activity on iCM either with or following cold cardioplegia. This effect is associated with ASC-S-mediated cellular clearance of reactive oxygen species. The effect of ASC-S on the temporal recovery of iCM function supports the possibility of lengthening heart storage by augmenting cardioplegic transport solution with ASC-S, expanding the pool of hearts for transplantation.

© 2020 AlphaMed Press.

Keywords: adipose stem cells; cardiac; cellular therapy; hypoxia; iPSC; pluripotent stem cells

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