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  • Perspective
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Regenerating the field of cardiovascular cell therapy

Nature Biotechnology volume 37, pages 232–237 (2019)Cite this article

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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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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

    Kenneth R. Chien & Jonas Frisén

  2. Department of Medicine, Karolinska Institutet, Stockholm, Sweden

    Kenneth R. Chien

  3. Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca Gothenburg, Gothenburg, Sweden

    Regina Fritsche-Danielson

  4. Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA

    Douglas A. Melton

  5. Howard Hughes Medical Institute, Chevy Chase, MD, USA

    Douglas A. Melton

  6. Departments of Pathology, Bioengineering and Medicine/Cardiology, Institute for Stem Cell and Regenerative Medicine, Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA

    Charles E. Murry

  7. Institute for Stem Cell Biology and Regenerative Medicine; Ludwig Center for Cancer Stem Cell Biology and Medicine; Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA

    Irving L. Weissman

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

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Competing interests

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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