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REGENERATION

Defining the pathways of heart regeneration

Nature Cell Biology volume 24, pages 606–607 (2022)Cite this article

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Although cardiac cell therapy has been intensely studied, the high expectations are still an unmet goal. A study now characterizes the translational potential and mode of action of human ventricular progenitors (HVPs) derived from embryonic stem cells, as a source for cardiac cell therapy.

Cardiac cell therapy, aiming to treat acute myocardial infarction or heart failure, has been an area of pre-clinical and clinical research for several decades. The first clinical application of cell therapy to treat the heart dates back to more than 20 years ago1. Since then, a multitude of clinical trials have been conducted, but given the inconsistent or at best moderately positive effects reported2,3,4, the high expectations for cardiac cell therapy have so far not been met. These studies predominantly used bone marrow cells and while the lack of efficacy might simply be due to the inability of these cells to restore cardiac function, it might also be explained by the lack of fundamental understanding of the mode of action of the cells or a wrongful use in the trial itself. Whereas cell therapy was initially proposed to result in the remuscularization of the injured heart, it was later shown that the cell sources used had no intrinsic capability of (trans)differentiating into functional cardiomyocytes (CMs) themselves5. Nonetheless, beneficial effects were reproducibly present in pre-clinical studies6 and these effects have been attributed to the fact that injection of bone marrow cells was shown to trigger an acute sterile inflammatory response that affected the activity of cardiac fibroblasts and enhanced the mechanical properties of the injured area7. Despite open-ended mechanistic questions, the incredible therapeutic potential of the method and room for improvement provide support to further explore the effect of cell therapy on heart repair.

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Fig. 1: The proposed mode of action of HVP-mediated cardiac cell therapy.

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Authors and Affiliations

  1. Hubrecht Institute, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands

    Louk Theodoor Timmer & Eva van Rooij

  2. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

    Eva van Rooij

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  1. Louk Theodoor Timmer
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  2. Eva van Rooij
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Correspondence to Eva van Rooij.

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The authors declare no competing interests.

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Timmer, L.T., van Rooij, E. Defining the pathways of heart regeneration. Nat Cell Biol 24, 606–607 (2022). https://doi.org/10.1038/s41556-022-00914-y

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