title: Therapeutic potentials of umbilical cord-derived mesenchymal stromal cells for ischemic-type biliary lesions following liver transplantation.
abstract: Ischemic-type biliary lesions are severe, graft-threatening complications after orthotopic liver transplantation, and a novel and efficient therapeutic strategy is urgently needed. Due to the immunosuppressive and regenerative properties, mesenchymal stromal cells (MSCs) could be an interesting candidate.
  
  
  
  We initiated safety and efficacy of human umbilical cord-derived MSC (UC-MSC) transfusions for patients with ischemic-type biliary lesions after liver transplantation. From January 2013 to June 2014, 12 ischemic-type biliary lesions patients were recruited as the MSCs group in this phase I, prospective, single-center clinical study. Patients in this group received six doses of UC-MSCs (about 1.0 × 106MSCs per kilogram body weight through peripheral intravenous infusion). The traditional therapeutic protocol was applied during October 2003 to December 2012 in 70 ischemic-type biliary lesions patients who were treated as the control group. Liver function tests, the need for interventional therapies and graft survival rate were chosen to evaluate the therapeutic efficacy of MSC treatment. Adverse events were closely monitored up to 2 years after MSC transfusions.
  
  
  
  No significant MSC-related adverse events were observed during the trial. Compared with baseline, the levels of total bilirubin, γ-glutamyl transferase and alkaline phosphatase were decreased after UC-MSC treatment at week 20 and week 48. Interventional therapies were performed in 64.3% (45/70) of patients in the control group and 33.3% (4/12) of patients in the MSCs groups. MSC therapy significantly decreased the need for interventional therapies (P = 0.046). The 1- and 2-year graft survival rates were higher in the MSCs group (100% and 83.3%, respectively) than in the control group (72.9% and 68.6%, respectively).
  
  
  
  The UC-MSC transfusions are clinically safe and short-term favorable, which may become a novel treatment for patients with ischemic-type biliary lesions after liver transplantation.
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Cell-Gene Therapy Translational Medicine Research Center, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ying-Cai
authors.initials: YC
authors.lastname: Zhang
authors.affiliation: Guangdong Province Key Laboratory of Hepatology Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Bin-Sheng
authors.initials: BS
authors.lastname: Fu
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Wang
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Li
authors.affiliation: Department of Surgery Intensive Care Unit, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Yi
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Genshu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Yi
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Cell-Gene Therapy Translational Medicine Research Center, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Hepatology Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. Electronic address: keekee77@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. Electronic address: yysysu@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Liver Surgery and Liver Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Chen
mesh_terms: D000328:Adult; D001659:Biliary Tract / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006085:Graft Survival; D006801:Humans; D007511:Ischemia / Q000209:etiology* / Q000628:therapy*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D016896:Treatment Outcome; D014470:Umbilical Cord / Q000166:cytology*
keywords: ischemic-type biliary lesions; liver transplantation; mesenchymal stromal cells; umbilical cord