Details

Autor(en) / Beteiligte

• Bellamy, Valérie, MSc
• Vanneaux, Valérie, MD, PhD
• Bel, Alain, MD
• Nemetalla, Hany, MD
• Emmanuelle Boitard, Solène, MSc
• Farouz, Yohan, PhD
• Joanne, Pierre, PhD
• Perier, Marie-Cécile, MD
• Robidel, Estelle
• Mandet, Chantal
• Hagège, Albert, MD, PhD
• Bruneval, Patrick, MD, PhD
• Larghero, Jérôme, MD, PhD
• Agbulut, Onnik, PhD
• Menasché, Philippe, MD, PhD

Titel

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

Ist Teil von

• The Journal of heart and lung transplantation, 2015-09, Vol.34 (9), p.1198-1207

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.