Unlocking the Pragmatic Potential of Regenerative Therapies in Heart Failure with Next-Generation Treatments

Yoshikazu Kishino, Keiichi Fukuda

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)


Patients with chronic heart failure (HF) have a poor prognosis due to irreversible impairment of left ventricular function, with 5-year survival rates <60%. Despite advances in conventional medicines for HF, prognosis remains poor, and there is a need to improve treatment further. Cell-based therapies to restore the myocardium offer a pragmatic approach that provides hope for the treatment of HF. Although first-generation cell-based therapies using multipotent cells (bone marrow-derived mononuclear cells, mesenchymal stem cells, adipose-derived regenerative cells, and c-kit-positive cardiac cells) demonstrated safety in preclinical models of HF, poor engraftment rates, and a limited ability to form mature cardiomyocytes (CMs) and to couple electrically with existing CMs, meant that improvements in cardiac function in double-blind clinical trials were limited and largely attributable to paracrine effects. The next generation of stem cell therapies uses CMs derived from human embryonic stem cells or, increasingly, from human-induced pluripotent stem cells (hiPSCs). These cell therapies have shown the ability to engraft more successfully and improve electromechanical function of the heart in preclinical studies, including in non-human primates. Advances in cell culture and delivery techniques promise to further improve the engraftment and integration of hiPSC-derived CMs (hiPSC-CMs), while the use of metabolic selection to eliminate undifferentiated cells will help minimize the risk of teratomas. Clinical trials of allogeneic hiPSC-CMs in HF are now ongoing, providing hope for vast numbers of patients with few other options available.

Original languageEnglish
Article number915
Issue number3
Publication statusPublished - 2023 Mar


  • CM
  • cardiomyocyte
  • heart failure
  • hiPSC
  • human-induced pluripotent stem cell
  • iPSC
  • induced pluripotent stem cell

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology


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