Key result
Heart regeneration requires targeting fibroblasts, immune, and nervous cells beyond just muscle and blood vessels.
Why the study?
Heart regeneration research has predominantly focused on cardiomyocyte proliferation and angiogenesis, but the roles and crosstalk of non-muscle and non-vessel cells in repair remain less defined.
This review emphasizes the need for a combinatorial approach to heart regeneration that targets non-muscle and non-vessel cells, including fibroblasts, immune, conduction, and nervous system cells.
Challenges myocyte-centric paradigms in regeneration; leaves open optimal multicellular targets for clinical translation.
The most striking consequence of a heart attack is the loss of billions of heart muscle cells, alongside damage to the associated vasculature. The lost cardiovascular tissue is replaced by scar formation, which is non-functional and results in pathological remodelling of the heart and ultimately heart failure. It is, therefore, unsurprising that the heart regeneration field has centred efforts to generate new muscle and blood vessels through targeting cardiomyocyte proliferation and angiogenesis following injury. However, combined insights from embryological studies and regenerative models, alongside the adoption of -omics technology, highlight the extensive heterogeneity of cell types within the forming or re-forming heart and the significant crosstalk arising from non-muscle and non-vessel cells. In this review, we focus on the roles of fibroblasts, immune, conduction system, and nervous system cell populations during heart development and we consider the latest evidence supporting a function for these diverse lineages in contributing to regeneration following heart injury. We suggest that the emerging picture of neurologically, immunologically, and electrically coupled cell function calls for a wider-ranging combinatorial approach to heart regeneration.
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Sayers et al. (2020) conducted a review in Heart injury and regeneration. A combinatorial approach to heart regeneration targeting fibroblasts, immune, conduction, and nervous system cells is required beyond generating new muscle and blood vessels.
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