Extracellular vesicles for cardiac repair: A translational experience

IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Annales d'endocrinologie Pub Date : 2024-10-01 DOI:10.1016/j.ando.2024.08.039
MD, PhD Philippe Menasché
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Abstract

The increasing recognition that stem cells transplanted in the myocardium act primarily through the paracrine activation of endogenous repair pathways mediated by the release of vesicular and soluble components has led to consider that these products could represent stand-alone therapeutics. Compared with the parental cells, they feature the major advantage of lacking immunogenicity, at least when the secretome is derived from cardiovascular progenitor cells (CPC). We then started a program aimed at testing this secretome in patients with chronic heart failure. The translational steps entailed the reprogramming of blood cells of an healthy donor into induced pluripotent stem cells (iPSC), their differentiation in CPC, the collection of the conditioned medium which has then been purified and concentrated by tangential flow filtration before cryopreservation of the scaled-out vials. The EV-enriched secretome has also been extensively quality-controlled. We have now started to test this extracellular vesicle-enriched secretome of CPC in severe non-ischemic dilated cardiomyopathy (SECRET-HF, NCT05774509). By July, 2024, 3 patient have been treated without safety issues. While this trial demonstrates the clinical translatability of the concept, several key questions remain to be addressed, particularly: Can the therapeutic effects of the secretome be recapitulated by a limited number of its components? What are the optimal dosing metrics? Is a cardiac-targeting of the secretome mandatory for achieving a therapeutic effect following a systemic delivery? Ongoing and future experimental and clinical studies should help addressing these issues, thereby allowing to more accurately positioning EV-enriched secretomes within the armamentarium of therapies against heart failure.
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用于心脏修复的细胞外囊泡:转化经验
越来越多的人认识到,移植到心肌中的干细胞主要通过释放囊泡和可溶性成分来激活内源性修复途径,这促使人们考虑这些产品可以作为独立的治疗药物。与亲代细胞相比,它们的主要优点是没有免疫原性,至少在分泌组来自心血管祖细胞(CPC)时是如此。随后,我们启动了一项计划,旨在对慢性心力衰竭患者进行这种分泌组的测试。转化步骤包括将健康捐献者的血细胞重编程为诱导多能干细胞(iPSC),将其分化为 CPC,收集条件培养基,然后通过切向流过滤进行纯化和浓缩,最后冷冻保存。我们还对富集的 EV 分泌组进行了广泛的质量控制。目前,我们已开始在重度非缺血性扩张型心肌病患者中测试这种富含细胞外囊泡的 CPC 分泌组(SECRET-HF,NCT05774509)。截至 2024 年 7 月,已有 3 名患者接受了治疗,未出现安全问题。虽然这项试验证明了这一概念的临床可转化性,但仍有几个关键问题有待解决,特别是:分泌组的治疗效果能否通过其有限的几种成分来重现?最佳剂量指标是什么?分泌物组的心脏靶向性是否是在全身给药后实现治疗效果的必要条件?正在进行的和未来的实验和临床研究将有助于解决这些问题,从而更准确地将富含 EV 的分泌物定位为治疗心衰的药物。
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来源期刊
Annales d'endocrinologie
Annales d'endocrinologie 医学-内分泌学与代谢
CiteScore
4.40
自引率
6.50%
发文量
311
审稿时长
50 days
期刊介绍: The Annales d''Endocrinologie, mouthpiece of the French Society of Endocrinology (SFE), publishes reviews, articles and case reports coming from clinical, therapeutic and fundamental research in endocrinology and metabolic diseases. Every year, it carries a position paper by a work-group of French-language endocrinologists, on an endocrine pathology chosen by the Society''s Scientific Committee. The journal is also the organ of the Society''s annual Congress, publishing a summary of the symposia, presentations and posters. "Les Must de l''Endocrinologie" is a special booklet brought out for the Congress, with summary articles that are always very well received. And finally, we publish the high-level instructional courses delivered during the Henri-Pierre Klotz International Endocrinology Days. The Annales is a window on the world, keeping alert clinicians up to date on what is going on in diagnosis and treatment in all the areas of our specialty.
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