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Myocardial regenerative therapy using a scaffold-free skeletal-muscle-derived cell sheet in patients with dilated cardiomyopathy even under a left ventricular assist device: a safety and feasibility study

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Abstract

Background and purpose

Despite promising experimental results, clinically, intramyocardial myoblast injection failed to reverse remodeling and it induced arrhythmogenicity. In contrast, scaffold-free skeletal muscle-derived cell (SC) sheets attenuated cardiac dysfunction and arrhythmogenicity via paracrine effects. We report the first clinical trial of SC sheet implantation (SCSI) conducted in four patients with dilated cardiomyopathy (DCM) supported by a left ventricular assist device (LVAD).

Methods

SC sheets were made from muscle fibers and multi-layered SC sheets were applied to the left ventricular (LV) anterolateral surface via left thoracotomy.

Results

There were no major cardiac adverse events. Ventricular arrhythmia decreased in all except one patient, in whom global LV function did not improve. The LV volume decreased and LV ejection fraction improved in all except the same patient. Systolic wall thickening, reflecting regional wall motion, improved in the sheet-implanted areas, and vessels in the LV apex increased in all patients, suggesting angiogenesis. The LVAD was successfully removed in two patients.

Conclusions

SCSI induced reverse remodeling and angiogenesis, and improved LV function, allowing LVAD removal in two patients, although functional recovery failed to improve in the one non-responder, even with angiogenesis. SCSI is a promising regenerative therapy for DCM patients responsive to this strategy, even with LVAD assistance.

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Acknowledgements

We thank Mr. Akima Harada for his excellent technical assistance.

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 (E1) Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yasushi Yoshikawa, Shigeru Miyagawa, Koichi Toda, Atsuhiro Saito & Yoshiki Sawa

  2. Department of Cardiology, Osaka University Graduate School of Medicine, Osaka, Japan

    Yasushi Sakata

Authors
  1. Yasushi Yoshikawa
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  2. Shigeru Miyagawa
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  3. Koichi Toda
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  4. Atsuhiro Saito
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  5. Yasushi Sakata
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  6. Yoshiki Sawa
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Corresponding author

Correspondence to Yoshiki Sawa.

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Conflict of interest

UMIN study Identifier: UMIN000000660. All authors served as investigators in this trial.

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Yoshikawa, Y., Miyagawa, S., Toda, K. et al. Myocardial regenerative therapy using a scaffold-free skeletal-muscle-derived cell sheet in patients with dilated cardiomyopathy even under a left ventricular assist device: a safety and feasibility study. Surg Today 48, 200–210 (2018). https://doi.org/10.1007/s00595-017-1571-1

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  • DOI: https://doi.org/10.1007/s00595-017-1571-1

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