Long-term functional benefits of human embryonic stem cell-derived cardiac progenitors embedded into a fibrin scaffold

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:34

Article

Bellamy, Valerie¹  Vanneaux, Valerie^2,3  Bel, Alain^1,4  Nemetalla, Hany^1,5  Boitard, Solene Emmanuelle⁶  Farouz, Yohan¹  Joanne, Pierre⁶  Perier, Marie-Cecile¹  Robidel, Estelle¹  Mandet, Chantal¹  Hagege, Albert^1,5  Bruneval, Patrick^1,7  Larghero, Jerome^2,3  Agbulut, Onnik⁶  Menasche, Philippe^1,4 

[1] Hop Europeen Georges Pompidou, INSERM U970, F-75015 Paris, France

[2] Univ Sorbonne Paris Cite, Hop St Louis, AP HP, Cell Therapy Unit, Paris, France

[3] Univ Sorbonne Paris Cite, Clin Invest Ctr Biotherapies CBT501, INSERM UMR1160, Paris, France

[4] Univ Sorbonne Paris Cite, Hop Europeen Georges Pompidou, AP HP, Dept Cardiovasc Surg, Paris, France

[5] Univ Sorbonne Paris Cite, Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France

[6] Univ Paris 06, Sorbonne Univ, IBPS, UMR CNRS 8256,Biol Adaptat & Ageing, Paris, France

[7] Univ Sorbonne Paris Cite, Hop Europeen Georges Pompidou, AP HP, Dept Pathol, Paris, France

关键词: stem cells;    heart failure;    tissue engineering;    cardiac progenitors;    cell transplantation;    embryonic stem cells;    cardiac patches;   

DOI  :  10.1016/j.healun.2014.10.008

来源: Elsevier

【 摘 要 】

BACKGROUND: Cardiac-committed cells and biomimetic scaffolds independently improve the therapeutic efficacy of stem cells. In this study we tested the long-term effects of their combination. METHODS: Eighty immune-deficient rats underwent permanent coronary artery ligation. Five to 7 weeks later, those with an echocardiographically measured ejection fraction (EF) <= 55% were re-operated on and randomly allocated to receive a cell-free fibrin patch (n = 25), a fibrin patch loaded with 700,000 human embryonic stem cells (ESC) pre-treated to promote early cardiac differentiation (SSEA-1(+) progenitors [n = 30]), or to serve as sham-operated animals (n = 25). Left ventricular function was assessed by echocardiography at baseline and every month thereafter until 4 months. Hearts were then processed for assessment of fibrosis and angiogenesis and a 5-component heart failure score was constructed by integrating the absolute change in left ventricular end-systolic volume (LVESV) between 4 months and baseline, and the quantitative polymerase chain reaction (qPCR)-based expression of natriuretic peptides A and B, myosin heavy chain 7 and periostin. All data were recorded and analyzed in a blinded manner. RESULTS: The cell-treated group consistently yielded better functional outcomes than the sham-operated group (p = 0.002 for EF; p = 0.01 for LVESV). Angiogenesis in the border zone was also significantly greater in the cell-fibrin group (p = 0.006), which yielded the lowest heart failure score (p = 0.04 vs sham). Engrafted progenitors were only detected shortly after transplantation; no grafted cells were identified after 4 months. There was no teratoma identified. CONCLUSIONS: A fibrin scaffold loaded with ESC-derived cardiac progenitors resulted in sustained improvement in contractility and attenuation of remodeling without sustained donor cell engraftment. A paracrine effect, possibly on innate reparative responses, is a possible mechanism for this enduring effect. (C) 2015 International Society for Heart and Lung Transplantation. All-rights reserved.

【 授权许可】

Free