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A Preconditioning Strategy to Augment Retention and Engraftment Rate of Donor Cells During Hepatocyte Transplantation.
Hsu, Yu-Chen; Yu, I-Shing; Tsai, Yu-Fei; Wu, Yao-Ming; Chen, You-Tzung; Sheu, Jin-Chuan; Lin, Shu-Wha.
Afiliação
  • Hsu YC; Liver Disease Prevention and Treatment Research Foundation, Taipei, Taiwan (R.O.C.).
  • Yu IS; Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).
  • Tsai YF; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).
  • Wu YM; Department of Surgery, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).
  • Chen YT; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).
  • Sheu JC; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).
  • Lin SW; Liver Disease Prevention and Treatment Research Foundation, Taipei, Taiwan (R.O.C.).
Transplantation ; 105(4): 785-795, 2021 04 01.
Article em En | MEDLINE | ID: mdl-32976366
BACKGROUND: Hepatocyte transplantation has been extensively investigated as an alternative to orthotopic liver transplantation. However, its application in routine clinical practice has been restricted because of low initial engraftment and subsequent repopulation. METHODS: Using mice as a model, we have developed a minimally invasive and nontoxic preconditioning strategy based on preadministration of antibodies against hepsin to increase donor hepatocyte retention and engraftment rate. RESULTS: Liver sinusoid diameters decreased significantly with antihepsin pretreatment, and graft cell numbers increased nearly 2-fold in the recipients' liver parenchyma for 20 days after hepatocyte transplantation. Postoperative complications such as hepatic ischemia injury or apparent immune cell accumulation were not observed in recipients. In a hemophilia B mouse model, antihepsin preconditioning enhanced the expression and clotting activity of coagulation factor IX (FIX) to nearly 2-fold that of immunoglobulin G-treated controls and maintained higher plasma FIX clotting activity relative to the prophylactic range for 50 days after hepatocyte transplantation. Antihepsin pretreatment combined with adeno-associated virus-transduced donor hepatocytes expressing human FIX-Triple, a hyperfunctional FIX variant, resulted in plasma FIX levels similar to those associated with mild hemophilia, which protected hemophilia B mice from major bleeding episodes for 50 days after transplantation. Furthermore, antihepsin pretreatment and repeated transplantation resulted in extending the therapeutic period by 30 days relative to the immunoglobulin G control. CONCLUSIONS: Thus, this antihepsin strategy improved the therapeutic effect of hepatocyte transplantation in mice with tremendous safety and minimal invasion. Taken together, we suggest that preconditioning with antihepsin may have clinical applications for liver cell therapy.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serina Endopeptidases / Transplante de Fígado / Condicionamento Pré-Transplante / Hepatócitos / Anticorpos Neutralizantes / Sobrevivência de Enxerto / Hemofilia A Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serina Endopeptidases / Transplante de Fígado / Condicionamento Pré-Transplante / Hepatócitos / Anticorpos Neutralizantes / Sobrevivência de Enxerto / Hemofilia A Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article