Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience.
Eur Heart J
; 36(12): 743-50, 2015 Mar 21.
Article
em En
| MEDLINE
| ID: mdl-24835485
ABSTRACT
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bancos de Tecidos
/
Separação Imunomagnética
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Células-Tronco Embrionárias Humanas
Tipo de estudo:
Diagnostic_studies
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Evaluation_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur Heart J
Ano de publicação:
2015
Tipo de documento:
Article