Peripheral infusion of human umbilical cord mesenchymal stem cells rescues acute liver failure lethality in monkeys.

Autor: Guo G; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China.; Department of Talent Highland, First Affiliated Hospital of Xi'an Jiao Tong University, Xian, 710061, China.; Department of General Surgery, First Affiliated Hospital of Xi'an Jiao Tong University, Xian, 710061, China., Zhuang X; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China.; Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China., Xu Q; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China., Wu Z; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China., Zhu Y; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China., Zhou Y; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China., Li Y; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China., Lu Y; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China., Zhang B; Sichuan Stem Cell Bank & Sichuan Neo-Life Stem Cell Biotech Inc., Chengdu, 610037, China., Talbot P; Department of Cell Biology & Neuroscience, University of California, Riverside, CA, 92521, USA.; The UCR Stem Cell Center and Core of University of California, Riverside, CA, 92521, USA., Liao J; The UCR Stem Cell Center and Core of University of California, Riverside, CA, 92521, USA.; Department of Bioengineering, University of California, Riverside, CA, 92521, USA., She J; Department of Talent Highland, First Affiliated Hospital of Xi'an Jiao Tong University, Xian, 710061, China.; Department of General Surgery, First Affiliated Hospital of Xi'an Jiao Tong University, Xian, 710061, China., Bu H; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China. hongbu@scu.edu.cn.; Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China. hongbu@scu.edu.cn., Shi Y; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China. shiyujun@scu.edu.cn.; Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China. shiyujun@scu.edu.cn.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2019 Mar 12; Vol. 10 (1), pp. 84. Date of Electronic Publication: 2019 Mar 12.
DOI: 10.1186/s13287-019-1184-2
Abstrakt: Background: Acute liver failure (ALF) is a complicated clinical syndrome associated with high mortality, with liver transplantation as the only treatment option. Treatment of mesenchymal stem cells has shown a potential therapeutic option for acute liver failure. However, the lack of random clinical trials and large non-human primate studies makes it necessary to assess the efficacy and safety in the clinic.
Methods: We treated the monkeys with peripheral delivery of human umbilical MSCs (hUC-MSCs) and investigated the role of hUC-MSCs in modulating the progress of acute liver failure.
Results: The use of early peripheral infusion of human umbilical cord MSC infusion did not improve liver regeneration or modulate adaptive immunity. However, it significantly suppressed the hepatic aggregation and maturation of circulating monocytes and their IL-6 secretion, greatly improving liver histology, systemic homeostasis, and survival.
Conclusions: Our study reveals the critical role of monocyte-derived IL-6 in initiating and accelerating acute liver failure and hUC-MSC treatment can disrupt the development of the inflammatory cascade by inhibiting monocyte activation. Early hUC-MSC treatment disrupts the development of the inflammatory cascade, indicating a potential clinical solution for acute liver failure.
Databáze: MEDLINE
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