Regenerating the field of cardiovascular cell therapy

Abstract

The retraction of >30 falsified studies by Anversa et al. has had a disheartening impact on the cardiac cell therapeutics field. The premise of heart muscle regeneration by the transdifferentiation of bone marrow cells or putative adult resident cardiac progenitors has been largely disproven. Over the past 18 years, a generation of physicians and scientists has lost years chasing these studies, and patients have been placed at risk with little scientific grounding. Funding agencies invested hundreds of millions of dollars in irreproducible work, and both academic institutions and the scientific community ignored troubling signals over a decade of questionable work. Our collective retrospective analysis identifies preventable problems at the level of the editorial and peer-review process, funding agencies and academic institutions. This Perspective provides a chronology of the forces that led to this scientific debacle, integrating direct knowledge of the process. We suggest a science-driven path forward that includes multiple novel approaches to the problem of heart muscle regeneration.

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Fig. 1: Timeline of fundamental findings and preclinical outcomes supporting or contradicting the notion of cardiac stem/progenitor cell therapy.

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Acknowledgements

The authors gratefully acknowledge the careful editing and review of the manuscript by M. Sahara of the Karolinska Institutet.

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Correspondence to Kenneth R. Chien or Jonas Frisén or Regina Fritsche-Danielson or Douglas A. Melton or Charles E. Murry or Irving L. Weissman.

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K.R.C. is a scientific founder and equity holder in Moderna Therapeutics and Procella Therapeutics, and chair of the External Science Panel for AstraZeneca. R.F.-D. is an employee of AstraZeneca. J.F. is an advisor to 10XGenomics. D.A.M. is cofounder of Semma Therapeutics. C.E.M. is a scientific founder and equity holder in Cytocardia. I.L.W. is a cofounder of, director of, stockholder in and consultant to Forty Seven Inc, a company currently devoted to cancer immunotherapies with antibodies to macrophage checkpoint inhibitors.

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Chien, K.R., Frisén, J., Fritsche-Danielson, R. et al. Regenerating the field of cardiovascular cell therapy. Nat Biotechnol 37, 232–237 (2019). https://doi.org/10.1038/s41587-019-0042-1

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