浅析类器官与肝脏再生研究进展

肝脏 ›› 2023, Vol. 28 ›› Issue (6): 637-639.

浅析类器官与肝脏再生研究进展

刘文明, 鄢和新

200001 上海交通大学医学院附属仁济医院麻醉科

收稿日期:2023-05-20 出版日期:2023-06-30 发布日期:2023-08-30

Received:2023-05-20 Online:2023-06-30 Published:2023-08-30

摘要/Abstract

摘要： 世界范围内肝脏疾病的负担逐年增加,肝移植是目前治疗终末期肝病唯一有效的治疗手段,但受限于供体短缺。再生医学因强调替代治疗而显示出巨大的应用前景,旨在采用正常的功能肝细胞替换受损的肝组织,而优质的种子细胞是其广泛应用的前提。肝脏类器官不仅是模拟人类生理学和病理学的最佳细胞模型,同时也是再生医学和转化应用的重要细胞来源。在这里,我们讨论现今肝脏三维类器官培养的各方面进展,以及它如何在体内、外重构肝胆系统,如何成为全球性新兴肝脏再生医学的焦点。本文概述了肝细胞、胆管细胞和非实质细胞类器官系统,并讨论它们的优势、局限性以及肝脏再生医学未来的发展方向。

关键词: 再生医学, 肝脏再生, 肝脏类器官, 胆管类器官, 非实质细胞类器官

刘文明, 鄢和新. 浅析类器官与肝脏再生研究进展[J]. 肝脏, 2023, 28(6): 637-639.

参考文献

[1] He J, Lu H, Zou Q, et al. Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish. Gastroenterology,2014,146:789-800 e8.
[2] Eisenstein M. Organoids: the body builders. Nature Methods,2018,15:19-22.
[3] Marsee A, Roos FJM, Verstegen MMA, et al. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell, 2021,28:816-832.
[4] Huch M, Gehart H, van Boxtel R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell,2015,160:299-312.
[5] Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature,2013,494:247-250.
[6] Peng WC, Logan CY, Fish M, et al. Inflammatory Cytokine TNFalpha Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture. Cell,2018,175:1607-1619 e15.
[7] Hu H, Gehart H, Artegiani B, et al. Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids. Cell,2018,175:1591-1606 e19.
[8] Tanimizu N, Ichinohe N, Sasaki Y, et al. Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo. Nat Commun,2021,12:3390.
[9] Takebe T, Sekine K, Enomura M, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature,2013,499:481-484.
[10] Koike H, Iwasawa K, Ouchi R, et al. Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary. Nature,2019,574:112-116.
[11] Ogawa M, Jiang JX, Xia S, et al. Generation of functional ciliated cholangiocytes from human pluripotent stem cells. Nat Commun,2021,12:6504.
[12] Sampaziotis F, Muraro D, Tysoe OC, et al. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science,2021,371:839-846.
[13] Lu WY, Bird TG, Boulter L, et al. Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nat Cell Biol,2015,17:971-983.
[14] Sampaziotis F, de Brito MC, Madrigal P, et al. Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat Biotechnol, 2015,33:845-852.
[15] Koui Y, Kido T, Ito T, et al. An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells. Stem Cell Reports,2017,9:490-498.
[16] Coll M, Perea L, Boon R, et al. Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis. Cell Stem Cell, 2018,23:101-113 e7.
[17] Ouchi R, Togo S, Kimura M, et al. Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids. Cell Metab,2019,30:374-384.e6.
[18] Hofer M, Lutolf MP. Engineering organoids. Nat Rev Mater,2021,6:402-420.
[19] Stevens KR, Scull MA, Ramanan V, et al. In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease. Sci Transl Med,2017,9:eaah5505.