Hao Yu: The Postdoctoral Research Station, School of Medicine, Nankai University, Tianjin 300071, China; Nankai University School of Medicine, Tianjin, China; National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China. Electronic address: yuhao@amcellgene.com.
Ying Feng: National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China.
Wenjing Du: The Postdoctoral Research Station, School of Medicine, Nankai University, Tianjin 300071, China; Nankai University School of Medicine, Tianjin, China; National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China.
Meng Zhao: National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China.
Honghong Jia: National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China.
Zhe Wei: National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China.
ShuLin Yan: National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China.
Zhongchao Han: National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China; Jiangxi Engineering Research Center for Stem Cell, Jiangxi Health-Biotech Stem Cell Technology Co., Ltd., Shangrao, Jiangxi Province 334000, China; Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Ltd., Beijing 100176, China; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Leisheng Zhang: Jiangxi Engineering Research Center for Stem Cell, Jiangxi Health-Biotech Stem Cell Technology Co., Ltd., Shangrao, Jiangxi Province 334000, China; Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Ltd., Beijing 100176, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province & NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, Gansu Province 730000, China.
Zongjin Li: The Postdoctoral Research Station, School of Medicine, Nankai University, Tianjin 300071, China; Nankai University School of Medicine, Tianjin, China. Electronic address: zongjinli@nankai.edu.cn.
Zhibo Han: National Engineering Research Center of Cell Products, AmCellGene Engineering Co., Ltd, Tianjin 300457, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, Tianjin 300457, China; Jiangxi Engineering Research Center for Stem Cell, Jiangxi Health-Biotech Stem Cell Technology Co., Ltd., Shangrao, Jiangxi Province 334000, China; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China. Electronic address: hanzhibo@amcellgene.com.
BACKGROUND AND PURPOSE: Umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) are advanced therapy medicinal products (ATMPs) and thus act as an alternative to liver transplantation for acute-on-chronic liver failure (ACLF). Therewith, we are aiming to evaluate the pharmacologyandpharmacokinetics of GMP-grade UC-MSCs products on carbon tetrachloride (CCl4)-induced ACLF mouse model and the concomitant therapeutic dose for intravenous administration. METHODS: For the purpose, the GMP-grade UC-MSCs products were transplanted intravenously into the aforementioned CCl4-induced ACLF NOD-SCID mouse model, and the therapeutic effect was evaluated with the aid of serological, biochemical and histological assessments. Meanwhile, the correlationshipbetween the treatment groups and other characteristics were determined by conducting principal component analysis (PCA). To further verify the spatio-temporal pharmacokinetics of UC-MSCs products on ACLF treatment, we took advantage of the bioluminescence imaging (BLI) technology with the dual-color fluorescence reporter construct (pLV-Fluc-eGFP). RESULTS: The biological characteristics of UC-MSCs products were in conformity with the International Society of Cell Therapy (ISCT) criteriaand the GMP requirements. ACLF mice with high dose of UC-MSCs treatment revealed significantly alleviated pathological manifestations with a dramatically improved survival rate, the alleviation of liver injury with reduced hepatic enzyme, inflammatory infiltration and inflammatory cytokines. Notably, UC-MSCs in ACLF mice displayed preferable homing and delayed attenuation in the damaged liver tissue. CONCLUSION: Collectively, our data indicated the feasibility of UC-MSC-based cytotherapy for ACLF model administration. Our findings have provided new references for pharmacologyandpharmacokinetics assessments, which will provide overwhelming evidence for pre-clinical study in vivo.
