DOI: 10.1002/ame2.70052
Achieving scalable expansion of therapeutic porcine hepatocytes in vivo through serial transplantation
Zhiqiang Han1
Xin Wang2
Dawei Yu3
Jing Wang3
Ke Sun4
Siqi Wang3
Ying Zhang3
Guihai Feng3
Wei Li5
Tang Hai4
Jilong Ren4
1.State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;University of Chinese Academy of Sciences,Beijing,China2.State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;University of Chinese Academy of Sciences,Beijing,China;Medical School,University of Chinese Academy of Sciences,Beijing,China3.State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing,China4.State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing,China;Beijing Farm Animal Research Center,Institute of Zoology,Chinese Academy of Sciences,Beijing,China5.State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;University of Chinese Academy of Sciences,Beijing,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing,China
摘要：The clinical application of hepatocyte transplantation has been significantly hindered by the scarcity of primary hepatocytes and the functional immaturity of in vitro-pro-duced hepatocytes.By performing serial allogeneic hepatocyte transplantation in CRISPR/Cas9-mediated Fah-knockout pigs,we successfully achieved large-scale ex-pansion of hepatocytes while maintaining their authentic biological characteristics.Particularly,the established model enables sustained in vivo liver reconstruction,concurrently ameliorating hepatic fibrosis and demonstrating functional microenvi-ronmental remodeling.Moreover,through comprehensive single-cell transcriptomic profiling of 52 418 hepatocytes across transplant generations(F0-F2),we discovered that the cellular composition of these transplanted hepatocytes is similar to that of wild-type hepatocytes.The regenerated liver exhibits all six major hepatic cell types identical to the wild-type counterparts,with the characteristic lobular zonation pat-terns well preserved.Our research provides valuable insights into the large-scale expansion of physiologically functional hepatocytes in vivo without compromising their biological properties.This finding holds great promise for advancing the clinical application of human hepatocyte transplantation,potentially offering more effective treatment options for patients with liver diseases.
机标关键词：serialthroughvivoachievingexpansionhepatocytesporcinescalable
论文发表日期：2025-07-30
在线出版日期：2025-09-28（本平台首次上网日期，不代表文献的发表时间）
页数：8( 1337-1344 )
英文信息