Heart in a Dish: From Traditional 2D Differentiation Protocols to Cardiac Organoids

Gustavo Ramirez-Calderon, Giovanni Colombo, Carlos A. Hernandez-Bautista, Veronica Astro, Antonio Adamo*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


Human pluripotent stem cells (hPSCs) constitute a valuable model to study the complexity of early human cardiac development and investigate the molecular mechanisms involved in heart diseases. The differentiation of hPSCs into cardiac lineages in vitro can be achieved by traditional two-dimensional (2D) monolayer approaches or by adopting innovative three-dimensional (3D) cardiac organoid protocols. Human cardiac organoids (hCOs) are complex multicellular aggregates that faithfully recapitulate the cardiac tissue’s transcriptional, functional, and morphological features. In recent years, significant advances in the field have dramatically improved the robustness and efficiency of hCOs derivation and have promoted the application of hCOs for drug screening and heart disease modeling. This review surveys the current differentiation protocols, focusing on the most advanced 3D methods for deriving hCOs from hPSCs. Furthermore, we describe the potential applications of hCOs in the pharmaceutical and tissue bioengineering fields, including their usage to investigate the consequences of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) infection in the heart.

Original languageEnglish (US)
Article number855966
JournalFrontiers in Cell and Developmental Biology
StatePublished - Feb 17 2022


  • cardiac development
  • cardiac differentiation
  • cardiac maturation
  • cardiogenesis
  • disease modeling
  • organoids
  • pluripotent stem cell (PSC)

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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