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转变心脏细胞治疗的观点:一项探索经心外膜注射外周血 CD34 细胞治疗严重 AMI 患者的非常长期临床结局的初步研究更新结果后的假说和评论。

Transforming Perspectives in Cardiac Cell Therapy: Hypothesis and Commentary Following Updated Results of a Pilot Study Investigating Very Long-Term Clinical Outcomes in Severe AMI Patients Following Trans-Epicardial Injection of Peripheral Blood CD34 Cells.

机构信息

Institut de Recherche en Hématologie Et Transplantation, Hôpital du Hasenrain, 87 Avenue d'Altkirch, 68100, Mulhouse, France.

CellProthera SAS, 12 Rue du Parc, 68100, Mulhouse, France.

出版信息

Stem Cell Rev Rep. 2024 Jan;20(1):247-257. doi: 10.1007/s12015-023-10643-w. Epub 2023 Oct 20.

Abstract

Ischemic heart attack is the leading cause of death worldwide. Ten percent of cases will die within an hour. Of the survivors, around 30% will have suffered a severe infarction which will lead to the irreparable destruction of 1 to 2 billion myocardial cells, causing an irreversible secondary heart failure with a poor prognosis in the short. The heart is a totally differentiated organ with a very low capacity for self-regeneration. No current treatment can prevent this fatal outcome, but only slow it down. For these reasons, cell therapy has generated enormous hope, but achieved somewhat disappointing results, depending on the type/source of cells which were used. From the end of 2002, our group conducted a Pilot study using immuno-selected autologous peripheral-blood (PB) CD34 cells in a small cohort of patients who had experienced a heart attack with poor prognosis. Three of these patients were immediately considered for heart transplant but lacked a readily available donor. CD34 cells were trans-epicardially delivered at the end of a coronary artery by-pass graft (CABG) operation without reperfusing the ischemic area, which was performed on a compassionate basis. All but one patient showed a marked and sustained improvement in their cardiac function parameters from the baseline values, associated with both cardiac tissue repair and revascularization, as demonstrated by PetScan examination. The patients' outcomes have been recently updated. Six out of seven patients have survived in good enough conditions for at least 12 years after cell therapy, including those three initially recommended for heart transplant and who have avoided it. Presently, five out of seven patients are still alive with an average follow-up of 17 years (range 16-20 years), which is very unusual after CABG for patients with such a poor initially prognosis.

摘要

缺血性心脏病发作是全球范围内的主要致死原因。其中 10%的病例会在发病后 1 小时内死亡。幸存者中,约有 30%会发生严重的梗塞,这将导致 1 亿至 2 亿心肌细胞不可逆转的破坏,导致短期内心力衰竭不可逆转且预后不良。心脏是一个完全分化的器官,自我再生能力非常低。目前没有任何治疗方法可以预防这种致命的后果,只能减缓其发展。出于这些原因,细胞疗法带来了巨大的希望,但结果却有些令人失望,这取决于所使用的细胞类型/来源。自 2002 年底以来,我们的团队在一组预后不良的心脏病发作患者中进行了一项使用免疫选择的自体外周血(PB)CD34 细胞的初步研究。其中 3 名患者立即考虑进行心脏移植,但缺乏现成的供体。CD34 细胞在冠状动脉旁路移植术(CABG)结束时通过心外膜输送,而不重新灌注缺血区域,这是基于同情的原则进行的。除了一名患者外,所有患者的心功能参数均从基线值显著且持续改善,这与心脏组织修复和再血管化有关,通过 PetScan 检查证实了这一点。患者的结局最近得到了更新。在细胞治疗后至少 12 年,7 名患者中有 6 名存活,且状况良好,其中包括最初建议进行心脏移植且已经避免移植的 3 名患者。目前,7 名患者中有 5 名仍存活,平均随访时间为 17 年(范围为 16-20 年),这在 CABG 治疗预后如此差的患者中非常罕见。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de12/10799833/4e2f9a4935bb/12015_2023_10643_Fig1_HTML.jpg

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