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Human cardiomyocyte progenitor cells differentiate into functional mature cardiomyocytes: an in vitro model for studying human cardiac physiology and pathophysiology

Abstract

To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is very low. Other methods to differentiate progenitor cells into beating cardiomyocytes rely on coculturing with rat neonatal cardiomyocytes, making it difficult to study human cardiomyocyte differentiation and (patho)physiology. Here we have developed a method for efficient isolation and expansion of human cardiomyocyte progenitor cells (CMPCs) from cardiac surgical waste or alternatively from fetal heart tissue. Furthermore, we provide a detailed in vitro protocol for efficient differentiation of CMPCs into cardiomyocytes with great efficiency (80–90% of differentiation). Once CMPCs are rapidly dividing (1 month after isolation), differentiation can be achieved in 3–4 weeks.

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Figure 1: Isolating CMPCs from human atrial tissue.
Figure 2: CMPC culture conditions.
Figure 3: Timeline of the differentiation procedure.
Figure 4: Cardiomyocyte differentiation indicated by staining sarcomeric structures.
Figure 5: Morphological characteristics of CMPCs during the differentiation procedure.

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Acknowledgements

This work was supported by a VIDI-grant (016.056.319, M.-J.G.) from The Netherlands Organization for Scientific Research (NWO), the Van Ruyven Foundation and BSIK program 'Dutch Program for Tissue Engineering.'

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Correspondence to Marie-José Goumans.

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Smits, A., van Vliet, P., Metz, C. et al. Human cardiomyocyte progenitor cells differentiate into functional mature cardiomyocytes: an in vitro model for studying human cardiac physiology and pathophysiology. Nat Protoc 4, 232–243 (2009). https://doi.org/10.1038/nprot.2008.229

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