期刊
JOURNAL OF HEART AND LUNG TRANSPLANTATION
卷 34, 期 9, 页码 1198-1207出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.healun.2014.10.008
关键词
stem cells; heart failure; tissue engineering; cardiac progenitors; cell transplantation; embryonic stem cells; cardiac patches
资金
- INSERM
- University Paris Descartes
- LabEx REVIVE
- Fondation de France
- LeDucq Foundation (SHAPEHEART network)
- Fondation de l'Avenir [ET2-658]
- Association Francaise contre les Myopathies [ANR-12-RPIB-0015]
- Fondation Lefoulon-Delalande
- Conseil Regional d'Ile de France (DIM Biotherapies)
- Fondation Coeur et Arteres
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.
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