Details

Autor(en) / Beteiligte

• Menasché, Philippe
• Vanneaux, Valérie
• Fabreguettes, Jean-Roch
• Bel, Alain
• Tosca, Lucie
• Garcia, Sylvie
• Bellamy, Valérie
• Farouz, Yohan
• Pouly, Julia
• Damour, Odile
• Périer, Marie-Cécile
• Desnos, Michel
• Hagège, Albert
• Agbulut, Onnik
• Bruneval, Patrick
• Tachdjian, Gérard
• Trouvin, Jean-Hugues
• Larghero, Jérôme

Titel

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

Ist Teil von

• European heart journal, 2015-03, Vol.36 (12), p.743-750

Ort / Verlag

England: Oxford University Press (OUP)

Erscheinungsjahr

2015

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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. 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. 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.