Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience

Eur Heart J. 2015 Mar 21;36(12):743-50. doi: 10.1093/eurheartj/ehu192. Epub 2014 May 16.


Aim: There is now compelling evidence that cells committed to a cardiac lineage are most effective for improving the function of infarcted hearts. This has been confirmed by our pre-clinical studies entailing transplantation of human embryonic stem cell (hESC)-derived cardiac progenitors in rat and non-human primate models of myocardial infarction. These data have paved the way for a translational programme aimed at a phase I clinical trial.

Methods and results: The main steps of this programme have included (i) the expansion of a clone of pluripotent hESC to generate a master cell bank under good manufacturing practice conditions (GMP); (ii) a growth factor-induced cardiac specification; (iii) the purification of committed cells by immunomagnetic sorting to yield a stage-specific embryonic antigen (SSEA)-1-positive cell population strongly expressing the early cardiac transcription factor Isl-1; (iv) the incorporation of these cells into a fibrin scaffold; (v) a safety assessment focused on the loss of teratoma-forming cells by in vitro (transcriptomics) and in vivo (cell injections in immunodeficient mice) measurements; (vi) an extensive cytogenetic and viral testing; and (vii) the characterization of the final cell product and its release criteria. The data collected throughout this process have led to approval by the French regulatory authorities for a first-in-man clinical trial of transplantation of these SSEA-1(+) progenitors in patients with severely impaired cardiac function.

Conclusion: Although several facets of this manufacturing process still need to be improved, these data may yet provide a useful platform for the production of hESC-derived cardiac progenitor cells under safe and cost-effective GMP conditions.

Keywords: Cell therapy; Heart failure; Myocardial infarction; Stem cells; Tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy / methods
  • Clinical Trials, Phase I as Topic
  • Cytogenetic Analysis
  • Evaluation Studies as Topic
  • Human Embryonic Stem Cells / transplantation*
  • Humans
  • Immunomagnetic Separation / methods*
  • Mice, SCID
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / transplantation
  • Tissue Banks / organization & administration*
  • Tissue Preservation / methods
  • Tissue Scaffolds