PMID- 25990469 OWN - NLM STAT- MEDLINE DCOM- 20160509 LR - 20220408 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 36 IP - 30 DP - 2015 Aug 7 TI - Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. PG - 2011-7 LID - 10.1093/eurheartj/ehv189 [doi] AB - 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. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author 2015. For permissions please email: journals.permissions@oup.com. FAU - Menasche, Philippe AU - Menasche P AD - Department of Cardiovascular Surgery, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, 20, rue Leblanc, Paris 75015, France University Paris Descartes, Sorbonne Paris Cite, Paris F-75475, France INSERM U970, Hopital Europeen Georges Pompidou, Paris, France philippe.menasche@egp.aphp.fr. FAU - Vanneaux, Valerie AU - Vanneaux V AD - Cell Therapy Unit, Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Paris F-75010, France INSERM, CIC de Biotherapies (CBT-501) and U1160, Institut Universitaire d'Hematologie, Hopital Saint-Louis, Paris 75010, France. FAU - Hagege, Albert AU - Hagege A AD - University Paris Descartes, Sorbonne Paris Cite, Paris F-75475, France INSERM U970, Hopital Europeen Georges Pompidou, Paris, France Department of Cardiology, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France. FAU - Bel, Alain AU - Bel A AD - Department of Cardiovascular Surgery, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, 20, rue Leblanc, Paris 75015, France. FAU - Cholley, Bernard AU - Cholley B AD - University Paris Descartes, Sorbonne Paris Cite, Paris F-75475, France Department of Anesthesiology and Intensive Care, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France. FAU - Cacciapuoti, Isabelle AU - Cacciapuoti I AD - Cell Therapy Unit, Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Paris F-75010, France INSERM, CIC de Biotherapies (CBT-501) and U1160, Institut Universitaire d'Hematologie, Hopital Saint-Louis, Paris 75010, France. FAU - Parouchev, Alexandre AU - Parouchev A AD - Cell Therapy Unit, Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Paris F-75010, France INSERM, CIC de Biotherapies (CBT-501) and U1160, Institut Universitaire d'Hematologie, Hopital Saint-Louis, Paris 75010, France. FAU - Benhamouda, Nadine AU - Benhamouda N AD - Department of Biological Immunology, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France. FAU - Tachdjian, Gerard AU - Tachdjian G AD - Assistance Publique-Hopitaux de Paris, University Paris Sud, Histology-Embryology-Cytogenetics, Hopitaux Universitaires Paris Sud, Clamart 92141, France. FAU - Tosca, Lucie AU - Tosca L AD - Assistance Publique-Hopitaux de Paris, University Paris Sud, Histology-Embryology-Cytogenetics, Hopitaux Universitaires Paris Sud, Clamart 92141, France. FAU - Trouvin, Jean-Hugues AU - Trouvin JH AD - University Paris Descartes, School of Pharmacy, Paris, France Pharmaceutical Innovation Department, Assistance Publique-Hopitaux de Paris, Central Pharmacy, Paris, France. FAU - Fabreguettes, Jean-Roch AU - Fabreguettes JR AD - Clinical Trials Department, Assistance Publique-Hopitaux de Paris, Central Pharmacy, Paris, France. FAU - Bellamy, Valerie AU - Bellamy V AD - INSERM U970, Hopital Europeen Georges Pompidou, Paris, France. FAU - Guillemain, Romain AU - Guillemain R AD - Department of Biological Immunology, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France. FAU - Suberbielle Boissel, Caroline AU - Suberbielle Boissel C AD - Assistance Publique-Hopitaux de Paris, Hopital Saint Louis, Laboratoire Regional d'Histocompatibilite Jean Dausset, Paris, France. FAU - Tartour, Eric AU - Tartour E AD - University Paris Descartes, Sorbonne Paris Cite, Paris F-75475, France INSERM U970, Hopital Europeen Georges Pompidou, Paris, France Department of Biological Immunology, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France. FAU - Desnos, Michel AU - Desnos M AD - University Paris Descartes, Sorbonne Paris Cite, Paris F-75475, France INSERM U970, Hopital Europeen Georges Pompidou, Paris, France Department of Cardiology, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France. FAU - Larghero, Jerome AU - Larghero J AD - Cell Therapy Unit, Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Paris F-75010, France INSERM, CIC de Biotherapies (CBT-501) and U1160, Institut Universitaire d'Hematologie, Hopital Saint-Louis, Paris 75010, France University Paris Diderot, Sorbonne Paris Cite, Paris F-75475, France. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150519 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 SB - IM MH - Female MH - Heart Failure/*therapy MH - Human Embryonic Stem Cells/*transplantation MH - Humans MH - Middle Aged MH - Myocardial Ischemia/therapy MH - Tissue Scaffolds MH - Treatment Outcome MH - Ventricular Dysfunction, Left/therapy OTO - NOTNLM OT - Cell therapy OT - Embryonic stem cells OT - Heart failure EDAT- 2015/05/21 06:00 MHDA- 2016/05/10 06:00 CRDT- 2015/05/21 06:00 PHST- 2015/03/07 00:00 [received] PHST- 2015/04/28 00:00 [accepted] PHST- 2015/05/21 06:00 [entrez] PHST- 2015/05/21 06:00 [pubmed] PHST- 2016/05/10 06:00 [medline] AID - ehv189 [pii] AID - 10.1093/eurheartj/ehv189 [doi] PST - ppublish SO - Eur Heart J. 2015 Aug 7;36(30):2011-7. doi: 10.1093/eurheartj/ehv189. Epub 2015 May 19.