Implantation of a Novel Allogeneic Mesenchymal Precursor Cell Type in Patients with Ischemic Cardiomyopathy Undergoing Coronary Artery Bypass Grafting: an Open Label Phase IIa Trial

Abstract

Heart failure is a life-limiting condition affecting over 40 million patients worldwide. Ischemic cardiomyopathy (ICM) is the most common cause. This study investigates in situ cardiac regeneration utilizing precision delivery of a novel mesenchymal precursor cell type (iMP) during coronary artery bypass surgery (CABG) in patients with ischemic cardiomyopathy (LVEF < 40 %). The phase IIa safety study was designed to enroll 11 patients. Preoperative scintigraphy imaging (SPECT) was used to identify hibernating myocardium not suitable for conventional myocardial revascularization for iMP implantation. iMP cells were implanted intramyocardially in predefined viable peri-infarct areas that showed poor perfusion, which could not be grafted due to poor target vessel quality. Postoperatively, SPECT was then used to identify changes in scar area. Intramyocardial implantation of iMP cells with CABG was safe with preliminary evidence of efficacy of improved myocardial contractility and perfusion of nonrevascularized territories resulting in a significant reduction in left ventricular scar area at 12 months after treatment. Clinical improvement was associated with a significant improvement in quality of life at 6 months posttreatment in all patients. The results suggest the potential for in situ myocardial regeneration in ischemic heart failure by delivery of iMP cells.

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Change history

  • 18 February 2020

    The Editor-in-Chief is currently investigating this article (Anastasiadis et al. 2016) as concerns have been raised about the ethics and regulatory approvals related to the cells used in the research. Further editorial action will be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full.

Abbreviations

CABG:

Coronary artery bypass grafting

ICM:

Ischemic cardiomyopathy

IRB:

Institutional review board

LAL:

Limulus amebocyte lysate

LV:

Left ventricular

LVEF:

Left ventricular ejection fraction

MACCE:

Major adverse cardiac and cerebrovascular events

MHC:

Major histocompatibility class

MLHFQ:

Minnesota Living with Heart Failure Questionnaire

MMP:

Matrix metalloproteinase

MSC:

Mesenchymal stem cells

NYHA:

New York Heart Association

PCR:

Polymerase chain reaction

SPECT:

Single photon emission computed tomography

TIMP:

Tissue inhibitor of matrix metalloproteinase

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Acknowledgments

We would like to thank the molecular biologist Dr Nancy Piouka for her valuable contribution in the preparation and handling of the iMP cells.

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Correspondence to Polychronis Antonitsis.

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Sources of Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Disclosures

AR, MJE, and SS hold shares in Cell Therapy Limited.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Associate Editor Enrique Lara-Pezzi oversaw the review of this article

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Anastasiadis, K., Antonitsis, P., Westaby, S. et al. Implantation of a Novel Allogeneic Mesenchymal Precursor Cell Type in Patients with Ischemic Cardiomyopathy Undergoing Coronary Artery Bypass Grafting: an Open Label Phase IIa Trial. J. of Cardiovasc. Trans. Res. 9, 202–213 (2016). https://doi.org/10.1007/s12265-016-9686-0

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Keywords

  • Ischemic cardiomyopathy
  • Coronary artery bypass grafting
  • Stem cells
  • Allogeneic
  • Mesenchymal
  • Heart failure