title: Transplantation of co-microencapsulated hepatocytes and HUVECs for treatment of fulminant hepatic failure.
abstract: OBJECTIVE
  Microencapsulated hepatocytes might solve immunological rejection, broadening a new perspective for the treatment of fulminant hepatic failure (FHF). However, the transplantation of microcapsulated hepatocytes is limited by low cell viability. Nevertheless, the co-microencapsulation of hepatocytes and human umbilical vein endothelial cells (HUVECs) may make the treatment of FHF more promising.
  
  
  METHODS
  We prepared the microcapsules using the high-voltage electrostatic droplet spray method, transplanted the empty microcapsules, isolated hepatocytes, microcapsulated hepatocytes, and co-microencapsulated hepatocytes and HUVEC intraperitoneally into rat models of FHF induced by D-aminogalactose (D-gal). After 1, 3, and 7 days, and 2, 3, and 4 weeks posttransplantation, we calculated the mortality and assessed alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) levels in the serum of the model; evaluated the integrality and recovery of microcapsules; and stained with hematoxylin and eosin (H&E) the recovered microcapsules as well as the liver of the FHF rats.
  
  
  RESULTS
  Hepatocyte-specific functions, including the levels of ALT, AST, and ALB in the serum of the co-microencapsulation group, were significantly better than those in the other groups (p<0.05) from 2 to 4 weeks after transplantation. Moreover, cotransplantation of the microencapsulated hepatocytes and HUVECs decreased the mortality rate of the FHF rats. The recovered microcapsules were intact, and recovery was up to 90%. H&E staining showed that the microencapsulated cells were still alive, and the liver tissues had started to recover after 4 weeks posttransplantation.
  
  
  CONCLUSIONS
  The microcapsules have good biocompatibility and immunoprotection to protect the hepatocytes from immunological rejection. Cotransplantation of the microencapsulated hepatocytes and HUVECs could decrease mortality rates and improve liver function in FHF.
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing-PR China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Qiu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wen
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Lin
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Du
authors.forename: Cuimi
authors.initials: C
authors.lastname: Duan
authors.forename: Chunren
authors.initials: C
authors.lastname: Wang
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005688:Galactosamine; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D061307:Human Umbilical Vein Endothelial Cells / Q000637:transplantation*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D012709:Serum Albumin; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase