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在接受体外膜肺氧合(ECMO)支持的终末期间质性肺病儿科患者中连续支气管内给予沃顿胶源性间充质基质细胞:一项安全性和可行性研究(CIBA方法)

Consecutive intrabronchial administration of Wharton's jelly-derived mesenchymal stromal cells in ECMO-supported pediatric patients with end-stage interstitial lung disease: a safety and feasibility study (CIBA method).

作者信息

Dominguez-Pinilla Nerea, González-Granado Luis Ignacio, Gonzaga Aitor, López Diaz María, Castellano Yáñez Cecilia, Aymerich Clara, Freire Xabier, Ordoñez Olga, Diaz de Atauri Álvaro Gimeno, Albi Rodríguez María Salomé, Martínez López Elisa, Iñiguez Rodrigo, Serrano Garrote Olga, Frontiñán Almudena Castro, Andreu Etelvina, Gutierrez-Vilchez Ana María, Anton-Bonete Marga, Martinez-Navarrete Gema, Castillo-Flores Nerea, Prat-Vidal Cristina, Blanco Margarita, Morante Valverde Rocío, Fernandez Eduardo, Querol Sergi, Hernández-Blasco Luis Manuel, Belda-Hofheinz Sylvia, Soria Bernat

机构信息

Pediatric Hematology and Oncology, Hospital 12 de Octubre, Madrid, Spain.

Immunodeficiencies Unit, Hospital 12 de Octubre, Madrid, Spain.

出版信息

Stem Cell Res Ther. 2025 Apr 5;16(1):164. doi: 10.1186/s13287-025-04289-3.

Abstract

BACKGROUND

Patients ineligible for lung transplant with end-stage Interstitial Lung Disease (ILD) on Extra-Corporeal Membrane Oxygenation (ECMO) face an appalling prognosis with limited therapeutic options. Due to the beneficial effect of Mesenchymal Stromal Cells (MSC) on inflammatory, immunological and infectious diseases, cell therapy has been proposed as an option, but administration is hampered by the ECMO.

METHODS

Cryopreserved Wharton-jelly derived MSC (WJ-MSC) were conveniently diluted and directly applied consecutively on each lobule (5,1 ml = 10 cells) at a continuous slow rate infused over one hour via flexible bronchoscopy (Consecutive IntraBronchial Administration method, CIBA method).

RESULTS

Intrabronchial administration of MSC to a patient on ECMO was well tolerated by the patient even though it did not reverse the patient's ILD. This manuscript presents preliminary evidence from ongoing clinical trials program on Cell Therapy of Inflammatory, Immune and Infectious Diseases and, to our knowledge, is the first report of intrabronchial administration of MSC in a paediatric ECMO patient with ILD. Even more, MSC administered by this method do not reach the systemic circulation and do get blocked on ECMO membrane.

CONCLUSIONS

Direct intrabronchial administration of MSC in a patient on ECMO is feasible and safe, and may be a new avenue to be assayed in ECMO patients with inflammatory, immunological and infectious diseases of the lung.

摘要

背景

患有终末期间质性肺疾病(ILD)且不符合肺移植条件、正在接受体外膜肺氧合(ECMO)治疗的患者预后极差,治疗选择有限。由于间充质基质细胞(MSC)对炎症、免疫和感染性疾病具有有益作用,细胞治疗被提议作为一种选择,但ECMO阻碍了其给药。

方法

将冻存的源自沃顿胶的MSC(WJ-MSC)进行适当稀释,通过可弯曲支气管镜以连续缓慢的速率(连续支气管内给药法,CIBA法)在1小时内将其依次直接应用于每个肺叶(5.1毫升=10个细胞)。

结果

对一名接受ECMO治疗的患者进行支气管内MSC给药,患者耐受性良好,尽管并未逆转该患者的ILD。本手稿展示了正在进行的炎症、免疫和感染性疾病细胞治疗临床试验项目的初步证据,据我们所知,这是首例关于在患有ILD的儿科ECMO患者中进行支气管内MSC给药的报告。此外,通过这种方法给药的MSC未进入体循环,而是被ECMO膜阻断。

结论

在接受ECMO治疗的患者中直接进行支气管内MSC给药是可行且安全的,可能是一种在患有肺部炎症、免疫和感染性疾病的ECMO患者中值得尝试的新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/490b/11972491/b6d3a0e3df14/13287_2025_4289_Fig1_HTML.jpg

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