{"title":"The perspective for next-generation lung replacement therapies: functional whole lung generation by blastocyst complementation.","authors":"Dai Shimizu, Akihiro Miura, Munemasa Mori","doi":"10.1097/MOT.0000000000001169","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"340-348"},"PeriodicalIF":1.8000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Organ Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MOT.0000000000001169","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"TRANSPLANTATION","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: 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.
Recent findings: 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.
Summary: 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.
期刊介绍:
Current Opinion in Organ Transplantation is an indispensable resource featuring key, up-to-date and important advances in the field from around the world. Led by renowned guest editors for each section, every bimonthly issue of Current Opinion in Organ Transplantation delivers a fresh insight into topics such as stem cell transplantation, immunosuppression, tolerance induction and organ preservation and procurement. With 18 sections in total, the journal provides a convenient and thorough review of the field and will be of interest to researchers, surgeons and other healthcare professionals alike.