4.5 Review

Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies

Journal

DISEASE MODELS & MECHANISMS
Volume 10, Issue 9, Pages 1039-1059

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.030320

Keywords

Cardiac arrhythmia; Cardiometabolic disease; Cardiomyopathy; Disease model; Genetic cardiac disease; Pluripotent stem cell; hiPSC

Funding

  1. European Research Council (ERC) under the European Union [638030]
  2. Netherlands Organisation for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  3. ILLUMINATE) [91715303]
  4. ERC-AdG (STEMCARDIOVASC) grant [323182]
  5. European Research Council (ERC) [323182, 638030] Funding Source: European Research Council (ERC)

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It is now a decade since human induced pluripotent stem cells (hiPSCs) were first described. The reprogramming of adult somatic cells to a pluripotent state has become a robust technology that has revolutionised our ability to study human diseases. Crucially, these cells capture all the genetic aspects of the patient from which they were derived. Combined with advances in generating the different cell types present in the human heart, this has opened up new avenues to study cardiac disease in humans and investigate novel therapeutic approaches to treat these pathologies. Here, we provide an overview of the current state of the field regarding the generation of cardiomyocytes from human pluripotent stem cells and methods to assess them functionally, an essential requirement when investigating disease and therapeutic outcomes. We critically evaluate whether treatments suggested by these in vitro models could be translated to clinical practice. Finally, we consider current shortcomings of these models and propose methods by which they could be further improved.

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