Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis

IF 4.7 2区 医学 Q1 RESPIRATORY SYSTEM Respiratory Research Pub Date : 2024-04-18 DOI:10.1186/s12931-024-02795-1
Giulia Gazzaniga, Marta Voltini, Alessandro Carletti, Elisa Lenta, Federica Meloni, Domenica Federica Briganti, Maria Antonietta Avanzini, Patrizia Comoli, Mirko Belliato
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Abstract

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.
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间充质基质细胞作为一种新的治疗方法在急性呼吸窘迫综合征和肺纤维化中的潜在应用
尽管 COVID-19 的爆发及其并发症仍在调查之中,但炎症后肺纤维化(PF)已被描述为继发于 SARS-CoV2 感染的急性呼吸窘迫综合征(ARDS)的长期后遗症。然而,针对 ARDS 和 PF 患者的治疗策略仍然有限,而且不能显著延长患者的寿命。迄今为止,肺移植仍是治疗终末期肺功能不全的唯一确切方法。在过去几年中,大量临床前和临床研究表明,异体间充质干细胞(MSCs)可能是治疗多种肺部疾病的一种很有前景的方法,在 COVID-19 大流行期间,对其治疗 ARDS 和预防 PF 的潜力进行了研究。从 2020 年 4 月到 2022 年 4 月,我们对 6 名处于增殖晚期的 COVID-19 相关中度 ARDS 成人患者进行了治疗,最多两次相同剂量的第三方异体骨髓间充质干细胞(BM-MSCs)静脉输注,每次间隔 15 天。未出现重大不良反应。四名患者完成了治疗并在重症监护室出院,两名患者只接受了一剂间充质干细胞治疗,但因出现多器官功能障碍综合征(MODS)而死亡。与其他患者相反,所有四名幸存者的气体交换均有所改善(PaO2/FiO2 比率大于 200)。此外,间充质干细胞治疗后的 LDH 变化趋势在幸存者和死亡者之间存在显著差异。虽然还需要进一步的研究和共享方案,但间叶干细胞疗法的安全性已被反复证明,其在治疗ARDS和预防PF方面的潜力可能代表了一种新的治疗策略。
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来源期刊
Respiratory Research
Respiratory Research 医学-呼吸系统
自引率
1.70%
发文量
314
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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