The Ritchie Centre, The Hudson Institute of Medical Research, Clayton 3168, Victoria, Australia.
Department of Obstetrics and Gynaecology, Monash University, Clayton 3168, Victoria, Australia.
Stem Cells Transl Med. 2024 Aug 16;13(8):711-723. doi: 10.1093/stcltm/szae037.
Lung and brain injury that occurs during the perinatal period leads to lifelong disability and is often driven and/or exacerbated by inflammation. Human amniotic epithelial cells (hAEC), which demonstrate immunomodulatory, anti-fibrotic, and regenerative capabilities, are being explored as a therapeutic candidate for perinatal injury. However, limitations regarding scalable manufacturing, storage, transport, and dose-related toxicity have impeded clinical translation. Isolated therapeutic extracellular vesicles (EVs) from stem and stem-like cells are thought to be key paracrine mediators of therapeutic efficacy. The unique characteristics of EVs suggest that they potentially circumvent the limitations of traditional cell-based therapies. However, given the novelty of EVs as a therapeutic, recommendations around ideal methods of production, isolation, storage, and delivery have not yet been created by regulatory agencies. In this concise review, we discuss the pertinence and limitations of cell-based therapeutics in perinatal medicine. We also review the preclinical evidence supporting the use of therapeutic EVs for perinatal therapy. Further, we summarize the arising considerations regarding adequate cell source, biodistribution, isolation and storage methods, and regulatory roadblocks for the development of therapeutic EVs.
围产期肺和脑损伤会导致终身残疾，并且常常由炎症驱动和/或加重。具有免疫调节、抗纤维化和再生能力的人羊膜上皮细胞（hAEC）被探索作为围产期损伤的治疗候选物。然而，可扩展性制造、储存、运输和与剂量相关的毒性方面的限制阻碍了临床转化。分离自干细胞和类干细胞的治疗性细胞外囊泡（EVs）被认为是治疗功效的关键旁分泌介质。EVs 的独特特性表明，它们可能规避传统细胞疗法的限制。然而，鉴于 EVs 作为治疗方法的新颖性，监管机构尚未就理想的生产、分离、储存和递送方法制定建议。在这篇简明的综述中，我们讨论了细胞疗法在围产医学中的相关性和局限性。我们还回顾了支持使用治疗性 EVs 进行围产治疗的临床前证据。此外，我们总结了关于合适的细胞来源、生物分布、分离和储存方法以及治疗性 EVs 开发的监管障碍的出现考虑因素。
