编者按:Philippe Menasché教授为巴黎第五大学心胸外科教授,乔治蓬皮杜欧洲医院心力衰竭外科主任,法国国家卫生和医学研究所心血管疾病细胞疗法实验室的主任。其已在细胞疗法领域研究长达15余年,于2000年完成了世界首例严重心力衰竭患者进行心肌内移植自体骨骼肌成肌细胞的手术。在AHA年会现场,针对干细胞疗法,《国际循环》记者采访了Menasché教授。
采访精选:
心脏干细胞发挥功能获益的机制尚不十分清楚。然而,移植入人体的细胞并不能独立建立新的心肌组织,而是通过激活内源性信号通路促使一些细胞因子分泌,从而发挥心脏保护作用。这也是为何现在的主流假说是旁分泌假说的原因。
胚胎干细胞来源的心脏祖细胞研究刚开展不久,结果尚不方便透漏。但这种细胞有致敏性,会激发炎性反应。Menasché研究团队试图通过使用传统药物对这一特性进行短期的免疫抑制。这种处理后,细胞在植入人体数天、数周或数月,将不会被自身免疫系统清除,因为它们已在体内定植了足够长时间,能分泌一些细胞因子促进内源性修复。
The mechanisms by which cells are acting after cardiac progenitor cells have been transplanted into human body are not yet quite clear. However, it seems that the grafted cells do not really build a new myocardial tissue by themselves, but rather secrete factors which probably activate endogenous signaling pathways, leading to some forms of cardioprotection. That is why the predominant hypothesis is the paracrine hypothesis whereby cells secrete these factors, which will stimulate wound healing to some extent.
The study that we are starting with human embryonic stem cell derived progenitors is really starting, so I cannot comment on that now. It is clear that because these cells are allergenic, they will trigger an immune response. We try to control that by short periods of immune suppression based on conventional drugs. That being said, it may not be such an issue that after a couple of days or weeks or months, cells will be cleared by the immune system provided that they have initially resided in the tissue long enough to secrete the factors I was talking about which are supposed to foster endogenous repair pathways.