PMID- 35123555 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20220531 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 13 IP - 1 DP - 2022 Feb 5 TI - Human menstrual blood-derived stem cell transplantation suppresses liver injury in DDC-induced chronic cholestasis. PG - 57 LID - 10.1186/s13287-022-02734-1 [doi] LID - 57 AB - BACKGROUND: Cholestatic liver injury can lead to serious symptoms and prognoses in the clinic. Currently, an effective medical treatment is not available for cholestatic liver injury. Human menstrual blood-derived stem cells (MenSCs) are considered as an emerging treatment in various diseases. This study aimed to explore the treatment effect of MenSCs in cholestatic liver injury. METHODS: The treatment effect of MenSCs on chronic cholestatic liver injury was verified in 3,5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC)-induced C57/BL6 mice. Pathological, fibrosis area in the liver tissue and serum liver enzymes were tested. Proteomics and western blot were used to explore the related targets and molecular mechanisms. Adeno-associated virus (AAV) 9-infected mice were applied for verification. RESULTS: MenSCs markedly improved the survival rate of the DDC-treated mice (60% vs. 100%), and decreased the mouse serum aspartate aminotransferase (AST) (169.4 vs. 108.0 U/L, p < 0.001), alanine aminotransferase (ALT) (279.0 vs. 228.9 U/L, p < 0.01), alkaline phosphatase (ALP) (45.6 vs. 10.6 U/L, p < 0.0001), direct bilirubin (DBIL) (108.3 vs. 14.0 mumol/L, p < 0.0001) and total bilirubin (TBIL) (179.2 vs. 43.3 mumol/L, p < 0.0001) levels as well as intrahepatic cholestasis, bile duct dilation and fibrotic areas (16.12 vs. 6.57%, p < 0.05). The results further indicated that MenSCs repaired the DDC-induced liver tight junction (TJ) pathway and bile transporter (OATP2, BSEP and NTCP1) injury, thereby inhibiting COL1A1, alpha-SMA and TGF-beta1 activation by upregulating liver beta-catenin expression. CONCLUSIONS: MenSC transplantation could be an effective treatment method for cholestatic liver injury in mice. MenSCs may exhibit therapeutic effects by regulating beta-catenin expression. CI - (c) 2022. The Author(s). FAU - Yang, Ya AU - Yang Y AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Chen, Yanfei AU - Chen Y AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Zhao, Yalei AU - Zhao Y AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Ji, Feiyang AU - Ji F AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Zhang, Lingjian AU - Zhang L AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Tang, Shima AU - Tang S AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Zhang, Sainan AU - Zhang S AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Hu, Qingqing AU - Hu Q AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Li, Zuhong AU - Li Z AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Zhang, Fen AU - Zhang F AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Li, Qian AU - Li Q AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. FAU - Li, Lanjuan AU - Li L AUID- ORCID: 0000-0001-6945-0593 AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, China. ljli@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220205 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 SB - IM MH - Animals MH - Bile Ducts MH - Blood Cells MH - *Cholestasis/therapy MH - Humans MH - *Liver/metabolism MH - Menstruation MH - Mice MH - Stem Cell Transplantation PMC - PMC8817575 OTO - NOTNLM OT - Bile transporter OT - Chronic cholestatic liver injury OT - Mesenchymal stem cell OT - Tight junction COIS- The authors declare that they have no competing interests. EDAT- 2022/02/07 06:00 MHDA- 2022/03/25 06:00 PMCR- 2022/02/05 CRDT- 2022/02/06 20:25 PHST- 2021/09/16 00:00 [received] PHST- 2021/11/08 00:00 [accepted] PHST- 2022/02/06 20:25 [entrez] PHST- 2022/02/07 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2022/02/05 00:00 [pmc-release] AID - 10.1186/s13287-022-02734-1 [pii] AID - 2734 [pii] AID - 10.1186/s13287-022-02734-1 [doi] PST - epublish SO - Stem Cell Res Ther. 2022 Feb 5;13(1):57. doi: 10.1186/s13287-022-02734-1.