Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report: Figure 1

Menasché, Philippe; Vanneaux, Valérie; Hagège, Albert; Bel, Alain; Cholley, Bernard; Cacciapuoti, Isabelle; Parouchev, Alexandre; Benhamouda, Nadine; Tachdjian, Gérard; Tosca, Lucie; Trouvin, Jean‐Hugues; Fabreguettes, Jean-Roch; Bellamy, Valérie; Guillemain, R.; Boissel, C. Suberbielle; Tartour, Éric; Desnos, Michel; Larghero, Jérôme

doi:10.1093/eurheartj/ehv189

Cited by 393 publications

(265 citation statements)

References 31 publications

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“…Human PSCs are attractive because they can be differentiated with great efficiency into cardiomyocytes (CMs) [47], providing an unlimited supply of cardiomyocytelike cells in vitro, before transplantation. After a long period of preclinical and translational work, the first human trial, ESCORT [27], was initiated in 2013 with the first patient receiving purified ESC-derived cardiac progenitors (CD15 1 Isl-…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

2017

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Heart failure (HF), a common sequela of cardiovascular diseases, remains a staggering clinical problem, associated with high rates of morbidity and mortality worldwide. Advances in pharmacological, interventional, and operative management have improved patient care, but these interventions are insufficient to halt the progression of HF, particularly the end-stage irreversible loss of functional cardiomyocytes. Innovative therapies that could prevent HF progression and improve the function of the failing heart are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many potential gene-and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell-and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies. The principles and mechanisms of action of gene and cell therapies for HF are discussed along with the limitations of current approaches. Finally, we highlight the emerging technologies that hold promise to revolutionize the biological therapies for cardiovascular diseases. STEM CELLS 2017;35:1131-1140 SIGNIFICANCE STATEMENTInnovative therapies that could treat heart failure and improve the function of failing hearts are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many gene-and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell-and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies that have entered the clinical arena.

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Section: Embryonic Stem Cellsmentioning

confidence: 99%

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

2017

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“…Recently, Menasche et al initiated the first clinical trial for HF treatment using embryonic stem cell (ESC)-derived cardiac progenitors, and reported improved patient symptoms at 3 months post-operation. 4 However, practical questions need to be addressed before large-scale clinical trials. Herein, we focus on the recent progress in cardiac regenerative therapy using PSCs, including the remaining hurdles and potential approaches to circumventing them.…”

Section: Cardiac Differentiation Of Pscsmentioning

confidence: 99%

“…4 A patient with Class III HF caused by MI, refractory to conventional treatment, underwent coronary bypass surgery with hESC-CPC-infiltrated fibrin patch implantation. After 3 months, symptoms and cardiac function improved, and contraction at the implantation site was evident.…”

Section: Remaining Hurdlesmentioning

confidence: 99%

Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy

Ichimura

Shiba

2017

Circ J

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Pluripotent stem cells (PSCs) have gained interest for cell-based regenerative therapies because of their capacity to differentiate into most somatic cell types, including cardiomyocytes. Remarkable progress in the generation of PSC-derived cardiomyocytes has been made in this decade, and recent preclinical transplantation studies using various animal models have provided proof-of-principle for their use in heart regeneration. However, several obstacles preclude their effective and safe clinical application for cardiac repair, including the need for approaches that prevent tumorigenesis, arrhythmogenesis, and immune rejection. In this review, we focus on recent progress in the field of PSC-based cardiac regenerative therapy, including the remaining hurdles and potential approaches to circumventing them.

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“…Enfin, il ne faut pas sous-évaluer la variabilité biologique et des réactifs [12][13][14][15]. La validation de ces étapes est réalisée en concertation avec les agences réglementaires.…”

Section: Essais Cliniquesunclassified

“…Les cellules étant allogé-niques, les patients reçoivent une immunosuppression transitoire stoppée au bout d'un mois. Les premiers patients ont été inclus dans cet essai, destiné avant tout à évaluer la tolérance et la sécurité des procédures et matériels, et il se déroule à ce jour sans incident [12,13]. Cet essai est donc particulièrement innovant, car il repose sur l'utilisation de cellules pluripotentes spéci-fiées et sélectionnées, en combinaison avec un biomaté-riau, et il mise autant, sinon davantage, sur la production de facteurs à activité paracrine par les cellules que sur leur intégration structurale au myocarde.…”

Section: Délivrance Des Cellules Biomatériaux Et Suivi Des Cellulesunclassified

Thérapies cellulaires des cardiopathies

Vilquin¹,

Etienne²

2016

Med Sci (Paris)

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L’insuffisance cardiaque est un problème majeur de santé publique et différentes approches de thérapie cellulaire sont expérimentées pour améliorer la fonction de myocardes défaillants. De nombreux types cellulaires ont été utilisés (myoblastes squelettiques, cellules hématopoïétiques, endothéliales ou mésenchymateuses, cellules d’origine cardiaque…), plus souvent dans des indications d’insuffisance post-ischémique que de cardiomyopathie dilatée génétique. Il est en effet plus aisé de cibler une zone de réparation localisée que l’ensemble du tissu myocardique. De nombreux essais cliniques ont fait état de résultats fonctionnels de faibles ampleurs mais encourageants, dont l’interprétation est souvent limitée par la taille des cohortes et les variabilités biologiques liées aux patients et aux candidats cellulaires. Ces essais ont aussi mis en lumière des mécanismes d’action inattendus, qui changent les concepts et méthodologies de traitement. En effet, les bénéfices proviendraient de sécrétions de facteurs trophiques, plutôt que d’une intégration structurale des cellules au sein du myocarde. Par conséquent, les nouvelles générations d’essais visent à accroître la taille et l’homogénéité des cohortes de patients afin d’améliorer la puissance statistique. Par ailleurs, des études misent sur l’accompagnement et/ou le conditionnement des cellules à l’aide de biomatériaux et/ou de cocktails de cytokines, en vue d’améliorer leur survie et leur fonctionnement. En parallèle, de nombreuses recherches en bio-ingénierie s’intéressent au soutien des cellules, au maintien de la structure du myocarde, à la fabrication ex vivo de tissu cardiaque de substitution, et finalement à la possibilité de remplacer les cellules par leurs produits actifs de sécrétion. Plusieurs dispositifs devraient émerger de ces recherches, dont le choix sera guidé par l’indication médicale.

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Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report: Figure 1

Cited by 393 publications

References 31 publications

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy

Thérapies cellulaires des cardiopathies

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