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Eur Heart J. 2015 Aug 7;36(30):2011-7. doi: 10.1093/eurheartj/ehv189. Epub 2015 May 19.

Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report.

Author information

1
Department of Cardiovascular Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 20, rue Leblanc, Paris 75015, France University Paris Descartes, Sorbonne Paris Cité, Paris F-75475, France INSERM U970, Hôpital Européen Georges Pompidou, Paris, France philippe.menasche@egp.aphp.fr.
2
Cell Therapy Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris F-75010, France INSERM, CIC de Biothérapies (CBT-501) and U1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris 75010, France.
3
University Paris Descartes, Sorbonne Paris Cité, Paris F-75475, France INSERM U970, Hôpital Européen Georges Pompidou, Paris, France Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
4
Department of Cardiovascular Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 20, rue Leblanc, Paris 75015, France.
5
University Paris Descartes, Sorbonne Paris Cité, Paris F-75475, France Department of Anesthesiology and Intensive Care, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
6
Department of Biological Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
7
Assistance Publique-Hôpitaux de Paris, University Paris Sud, Histology-Embryology-Cytogenetics, Hôpitaux Universitaires Paris Sud, Clamart 92141, France.
8
University Paris Descartes, School of Pharmacy, Paris, France Pharmaceutical Innovation Department, Assistance Publique-Hôpitaux de Paris, Central Pharmacy, Paris, France.
9
Clinical Trials Department, Assistance Publique-Hôpitaux de Paris, Central Pharmacy, Paris, France.
10
INSERM U970, Hôpital Européen Georges Pompidou, Paris, France.
11
Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Laboratoire Régional d'Histocompatibilité Jean Dausset, Paris, France.
12
University Paris Descartes, Sorbonne Paris Cité, Paris F-75475, France INSERM U970, Hôpital Européen Georges Pompidou, Paris, France Department of Biological Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
13
Cell Therapy Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris F-75010, France INSERM, CIC de Biothérapies (CBT-501) and U1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris 75010, France University Paris Diderot, Sorbonne Paris Cité, Paris F-75475, France.

Abstract

AIMS:

Comparative studies suggest that stem cells committed to a cardiac lineage are more effective for improving heart function than those featuring an extra-cardiac phenotype. We have therefore developed a population of human embryonic stem cell (ESC)-derived cardiac progenitor cells.

METHODS AND RESULTS:

Undifferentiated human ESCs (I6 line) were amplified and cardiac-committed by exposure to bone morphogenetic protein-2 and a fibroblast growth factor receptor inhibitor. Cells responding to these cardio-instructive cues express the cardiac transcription factor Isl-1 and the stage-specific embryonic antigen SSEA-1 which was then used to purify them by immunomagnetic sorting. The Isl-1(+) SSEA-1(+) cells were then embedded into a fibrin scaffold which was surgically delivered onto the infarct area in a 68-year-old patient suffering from severe heart failure [New York Heart Association [NYHA] functional Class III; left ventricular ejection fraction (LVEF): 26%]. A coronary artery bypass was performed concomitantly in a non-infarcted area. The implanted cells featured a high degree of purity (99% were SSEA-1(+)), had lost the expression of Sox-2 and Nanog, taken as markers for pluripotency, and strongly expressed Isl-1. The intraoperative delivery of the patch was expeditious. The post-operative course was uncomplicated either. After 3 months, the patient is symptomatically improved (NYHA functional Class I; LVEF: 36%) and a new-onset contractility is echocardiographically evident in the previously akinetic cell/patch-treated, non-revascularized area. There have been no complications such as arrhythmias, tumour formation, or immunosuppression-related adverse events.

CONCLUSION:

This observation demonstrates the feasibility of generating a clinical-grade population of human ESC-derived cardiac progenitors and combining it within a tissue-engineered construct. While any conclusion pertaining to efficacy would be meaningless, the patient's functional outcome yet provides an encouraging hint. Beyond this case, the platform that has been set could be useful for generating different ESC-derived lineage-specific progenies.

KEYWORDS:

Cell therapy; Embryonic stem cells; Heart failure

PMID:
25990469
DOI:
10.1093/eurheartj/ehv189
[Indexed for MEDLINE]

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