Jung-Taek Kang, Joo-Hee Park, Mi-Young Jung, Pu-Hyeon Cha, Choul Yong Park
{"title":"用新型脱细胞方法在GGTA1/CMAH/β4GalNT2敲除的猪角膜上建立基质角膜移植物。","authors":"Jung-Taek Kang, Joo-Hee Park, Mi-Young Jung, Pu-Hyeon Cha, Choul Yong Park","doi":"10.21037/atm-25-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diseases of the human cornea often necessitate corneal transplantation. However, donor corneas are not always readily available, leaving many patients waiting for donated corneas. Porcine corneas are a promising alternative to human donor corneas due to their close anatomical and physiological similarities. In this study, we produced <i>GGTA1</i>/<i>CMAH</i>/<i>β4GalNT2</i> knockout pigs [triple knockout (TKO)] to minimize immune rejection. We investigated the efficacy and safety of a novel corneal decellularization process using sodium cocoyl glutamate (SCG) and supernuclease (SN).</p><p><strong>Methods: </strong>We harvested cornea stromal grafts from 2-month-old TKO pigs, decellularized them using SCG and SN. The optical transparency, DNA content, collagen content, glycosaminoglycan content, and tensile strength of the decellularized corneas were measured. The <i>in vivo</i> safety and efficacy of the decellularized corneas were evaluated by transplanting them into the stromal pockets of rabbit corneas. Comparisons between wild type (WT) and TKO corneas, both decellularized and non-decellularized, were performed over a 4-week period post-transplantation.</p><p><strong>Results: </strong>Compared to a previous method using sodium N-lauroyl glutamate (SLG), the method using 0.5% SCG and SN more effectively removed DNA from the corneal stroma without significantly changing tensile strength, transparency, collagen, or glycosaminoglycan content. When decellularized corneas were implanted into corneal stromal pockets of rabbits, at 4 weeks post-surgery, decellularized corneas from WT pigs showed significant corneal neovascularization and opacity. In contrast, those from TKO pigs with 0.5% SCG plus SN decellularization maintained good transparency with minimal vascularization.</p><p><strong>Conclusions: </strong>Corneas from TKO pigs could be successfully decellularized using 0.5% SCG plus SN method, showing promising results after transplanting them into rabbit corneas.</p>","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 3","pages":"28"},"PeriodicalIF":0.0000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272801/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development of stromal corneal grafts using a novel decellularization method with sodium cocoyl glutamate on <i>GGTA1</i>/<i>CMAH</i>/<i>β4GalNT2</i> knock-out porcine corneas.\",\"authors\":\"Jung-Taek Kang, Joo-Hee Park, Mi-Young Jung, Pu-Hyeon Cha, Choul Yong Park\",\"doi\":\"10.21037/atm-25-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Diseases of the human cornea often necessitate corneal transplantation. However, donor corneas are not always readily available, leaving many patients waiting for donated corneas. Porcine corneas are a promising alternative to human donor corneas due to their close anatomical and physiological similarities. In this study, we produced <i>GGTA1</i>/<i>CMAH</i>/<i>β4GalNT2</i> knockout pigs [triple knockout (TKO)] to minimize immune rejection. We investigated the efficacy and safety of a novel corneal decellularization process using sodium cocoyl glutamate (SCG) and supernuclease (SN).</p><p><strong>Methods: </strong>We harvested cornea stromal grafts from 2-month-old TKO pigs, decellularized them using SCG and SN. The optical transparency, DNA content, collagen content, glycosaminoglycan content, and tensile strength of the decellularized corneas were measured. The <i>in vivo</i> safety and efficacy of the decellularized corneas were evaluated by transplanting them into the stromal pockets of rabbit corneas. Comparisons between wild type (WT) and TKO corneas, both decellularized and non-decellularized, were performed over a 4-week period post-transplantation.</p><p><strong>Results: </strong>Compared to a previous method using sodium N-lauroyl glutamate (SLG), the method using 0.5% SCG and SN more effectively removed DNA from the corneal stroma without significantly changing tensile strength, transparency, collagen, or glycosaminoglycan content. When decellularized corneas were implanted into corneal stromal pockets of rabbits, at 4 weeks post-surgery, decellularized corneas from WT pigs showed significant corneal neovascularization and opacity. In contrast, those from TKO pigs with 0.5% SCG plus SN decellularization maintained good transparency with minimal vascularization.</p><p><strong>Conclusions: </strong>Corneas from TKO pigs could be successfully decellularized using 0.5% SCG plus SN method, showing promising results after transplanting them into rabbit corneas.</p>\",\"PeriodicalId\":8216,\"journal\":{\"name\":\"Annals of translational medicine\",\"volume\":\"13 3\",\"pages\":\"28\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272801/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of translational medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/atm-25-3\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of translational medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/atm-25-3","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/13 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Development of stromal corneal grafts using a novel decellularization method with sodium cocoyl glutamate on GGTA1/CMAH/β4GalNT2 knock-out porcine corneas.
Background: Diseases of the human cornea often necessitate corneal transplantation. However, donor corneas are not always readily available, leaving many patients waiting for donated corneas. Porcine corneas are a promising alternative to human donor corneas due to their close anatomical and physiological similarities. In this study, we produced GGTA1/CMAH/β4GalNT2 knockout pigs [triple knockout (TKO)] to minimize immune rejection. We investigated the efficacy and safety of a novel corneal decellularization process using sodium cocoyl glutamate (SCG) and supernuclease (SN).
Methods: We harvested cornea stromal grafts from 2-month-old TKO pigs, decellularized them using SCG and SN. The optical transparency, DNA content, collagen content, glycosaminoglycan content, and tensile strength of the decellularized corneas were measured. The in vivo safety and efficacy of the decellularized corneas were evaluated by transplanting them into the stromal pockets of rabbit corneas. Comparisons between wild type (WT) and TKO corneas, both decellularized and non-decellularized, were performed over a 4-week period post-transplantation.
Results: Compared to a previous method using sodium N-lauroyl glutamate (SLG), the method using 0.5% SCG and SN more effectively removed DNA from the corneal stroma without significantly changing tensile strength, transparency, collagen, or glycosaminoglycan content. When decellularized corneas were implanted into corneal stromal pockets of rabbits, at 4 weeks post-surgery, decellularized corneas from WT pigs showed significant corneal neovascularization and opacity. In contrast, those from TKO pigs with 0.5% SCG plus SN decellularization maintained good transparency with minimal vascularization.
Conclusions: Corneas from TKO pigs could be successfully decellularized using 0.5% SCG plus SN method, showing promising results after transplanting them into rabbit corneas.
期刊介绍：
The Annals of Translational Medicine (Ann Transl Med; ATM; Print ISSN 2305-5839; Online ISSN 2305-5847) is an international, peer-reviewed Open Access journal featuring original and observational investigations in the broad fields of laboratory, clinical, and public health research, aiming to provide practical up-to-date information in significant research from all subspecialties of medicine and to broaden the readers’ vision and horizon from bench to bed and bed to bench. It is published quarterly (April 2013- Dec. 2013), monthly (Jan. 2014 - Feb. 2015), biweekly (March 2015-) and openly distributed worldwide. Annals of Translational Medicine is indexed in PubMed in Sept 2014 and in SCIE in 2018. Specific areas of interest include, but not limited to, multimodality therapy, epidemiology, biomarkers, imaging, biology, pathology, and technical advances related to medicine. Submissions describing preclinical research with potential for application to human disease, and studies describing research obtained from preliminary human experimentation with potential to further the understanding of biological mechanism underlying disease are encouraged. Also warmly welcome are studies describing public health research pertinent to clinic, disease diagnosis and prevention, or healthcare policy. With a focus on interdisciplinary academic cooperation, ATM aims to expedite the translation of scientific discovery into new or improved standards of management and health outcomes practice.
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