Columbia Center for Human Development and Division of Pulmonary, Allergy, Critical Care, Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Curr Opin Organ Transplant. 2024 Oct 1;29(5):340-348. doi: 10.1097/MOT.0000000000001169. Epub 2024 Jul 30.
Blastocyst complementation represents a promising frontier in next-generation lung replacement therapies. This review aims to elucidate the future prospects of lung blastocyst complementation within clinical settings, summarizing the latest studies on generating functional lungs through this technique. It also explores and discusses host animal selection relevant to interspecific chimera formation, a challenge integral to creating functional human lungs via blastocyst complementation.
Various gene mutations have been utilized to create vacant lung niches, enhancing the efficacy of donor cell contribution to the complemented lungs in rodent models. By controlling the lineage to induce gene mutations, chimerism in both the lung epithelium and mesenchyme has been improved. Interspecific blastocyst complementation underscores the complexity of developmental programs across species, with several genes identified that enhance chimera formation between humans and other mammals.
While functional lungs have been generated via intraspecies blastocyst complementation, the generation of functional interspecific lungs remains unrealized. Addressing the challenges of controlling the host lung niche and selecting host animals relevant to interspecific barriers between donor human and host cells is critical to enabling the generation of functional humanized or entire human lungs in large animals.
囊胚互补代表了下一代肺替代疗法的一个有前途的前沿领域。本综述旨在阐明肺囊胚互补在临床环境中的未来前景，总结通过该技术生成功能性肺的最新研究。它还探讨并讨论了与种间嵌合体形成相关的宿主动物选择，这是通过囊胚互补创建功能性人肺所必需的挑战。
各种基因突变已被用于创建空的肺巢，增强供体细胞对啮齿动物模型中互补肺的贡献效果。通过控制谱系来诱导基因突变，可以改善肺上皮和间充质中的嵌合性。种间囊胚互补强调了跨物种发育程序的复杂性，已经确定了几个基因可以增强人类和其他哺乳动物之间的嵌合体形成。
虽然已经通过种内囊胚互补生成了功能性肺，但尚未实现功能性种间肺的生成。控制宿主肺巢和选择与供体人类和宿主细胞之间的种间障碍相关的宿主动物对于在大型动物中生成功能性人源化或整个人类肺至关重要。
