Details

Autor(en) / Beteiligte

• Ménard, Claudine
• Hagège, Albert A
• Agbulut, Onnik
• Barro, Marietta
• Morichetti, Miguel Cortes
• Brasselet, Camille
• Bel, Alain
• Messas, Emmanuel
• Bissery, Alvine
• Bruneval, Patrick
• Desnos, Michel
• Pucéat, Michel
• Menasché, Philippe

Titel

Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study

Ist Teil von

• The Lancet (British edition), 2005-09, Vol.366 (9490), p.1005-1012

Ort / Verlag

London: Elsevier Ltd

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model. We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation. Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9·9% (range −20 to 0·3) relative to baseline (p=0·011) whereas in the treated group it improved by 6·6% (−5·7 to 50·8; comparison between groups p=0·002). These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.