Allan Katelin M, Farrow Nigel, Donnelley Martin, Jaffe Adam, Waters Shafagh A
School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC), University of New South Wales and Sydney Children's Hospital, Sydney, Australia.
Front Pharmacol. 2021 Mar 16;12:639475. doi: 10.3389/fphar.2021.639475. eCollection 2021.
Prognosis of patients with cystic fibrosis (CF) varies extensively despite recent advances in targeted therapies that improve CF transmembrane conductance regulator (CFTR) function. Despite being a multi-organ disease, extensive lung tissue destruction remains the major cause of morbidity and mortality. Progress towards a curative treatment strategy that implements a gene addition-technology to the patients' lungs has been slow and not yet developed beyond clinical trials. Improved delivery vectors are needed to overcome the body's defense system and ensure an efficient and consistent clinical response before gene therapy is suitable for clinical care. Cell-based therapy-which relies on functional modification of allogenic or autologous cells , prior to transplantation into the patient-is now a therapeutic reality for various diseases. For CF, pioneering research has demonstrated proof-of-principle for allogenic transplantation of cultured human airway stem cells into mouse airways. However, applying a cell-based therapy to the human airways has distinct challenges. We review CF gene therapies using viral and non-viral delivery strategies and discuss current advances towards autologous cell-based therapies. Progress towards identification, correction, and expansion of a suitable regenerative cell, as well as refinement of pre-cell transplant lung conditioning protocols is discussed.
尽管靶向治疗取得了最新进展，改善了囊性纤维化跨膜传导调节因子（CFTR）的功能，但囊性纤维化（CF）患者的预后仍存在很大差异。尽管CF是一种多器官疾病，但广泛的肺组织破坏仍然是发病和死亡的主要原因。采用基因添加技术治疗患者肺部的治愈性治疗策略进展缓慢，尚未超越临床试验阶段。在基因治疗适用于临床护理之前，需要改进递送载体以克服人体防御系统，并确保有效且一致的临床反应。基于细胞的疗法依赖于对同种异体或自体细胞进行功能修饰，然后再移植到患者体内，目前已成为多种疾病的治疗手段。对于CF，开创性研究已证明将培养的人气道干细胞异体移植到小鼠气道中的原理。然而，将基于细胞的疗法应用于人体气道面临着独特的挑战。我们回顾了使用病毒和非病毒递送策略的CF基因疗法，并讨论了自体细胞疗法的当前进展。还讨论了在识别、校正和扩增合适的再生细胞以及完善细胞移植前的肺预处理方案方面取得的进展。
