中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 12
Dec.  2023
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2023  >  39(12): 2851-2857

Efficacy of human umbilical cord mesenchymal stem cells via different transplantation approaches in treatment of rats with liver cirrhosis

DOI: 10.3969/j.issn.1001-5256.2023.12.016
  • 1.

    Clinical Research Center of Haikou People’s Hospital，Haikou 570208，China

  • 2.

    Shanghai Quansheng Bioengineering Co.，Ltd.，Shanghai 201401，China

Research funding:

National Health Commission Project： Stem Cell Clinical Research (MR-46-21-014648)

More Information
  • Corresponding author: JIANG Cuibao， jiangcuibao@xibaozhiliao.cn （ORCID： 0000-0001-6213-0829）
  • Received Date: 2022-11-21
  • Accepted Date: 2023-02-03
  • Published Date: 2023-12-12
    Abstract
  •   Objective  To investigate the therapeutic effect of the frozen and fresh preparations of human umbilical cord mesenchymal stem cells （hUC-MSC） on a rat model of liver cirrhosis after transplantation via the portal vein or the caudal vein.  Methods  A total of 70 specific pathogen-free healthy male Sprague-Dawley rats were randomly divided into normal group （13 rats fed with ordinary tap water and rat food） and liver cirrhosis model group （57 rats given subcutaneous multi-point injection of mixed carbon tetrachloride/olive oil solution）. At week 8， the growth of rats was observed for both groups， and 3 rats were selected from each group for histopathological examination to confirm the formation of liver cirrhosis. A total of 50 rats were selected from the liver cirrhosis model and were divided into model group， portal vein group+fresh cell preparation group， portal vein+frozen cell preparation group， caudal vein+fresh cell preparation group， and caudal vein+frozen cell preparation group using a random number table， with 10 rats in each group. Fresh or frozen hUC-MSC were transplanted via the portal vein or the caudal vein， and after 4 weeks of administration， the different groups were compared in terms of the changes in liver function parameters and liver fibrosis degree. Continuous data were expressed as mean±standard deviation， and the independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups.  Results  At week 8 of modeling， the model group showed the formation of pseudolobules of different sizes in the liver and met the diagnostic criteria for liver cirrhosis， with significant increases in the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBil）， and alkaline phosphatase （ALP） compared with the normal group （all P<0.001）， suggesting that the rat model of liver cirrhosis was established successfully. There were significant differences in the levels of ALT， AST， TBil， and ALP between the five groups （F=232.00， 177.10， 112.30， 121.70， all P<0.001）. Further comparison between two groups showed that the model group had significantly higher levels of ALT， AST， TBil， and ALP than the normal group （all P<0.01）， and the portal vein group+fresh cell preparation group， the portal vein+frozen cell preparation group， the caudal vein+fresh cell preparation group， and the caudal vein+frozen cell preparation group had significantly lower levels of ALT， AST， TBil， and ALP than the model group （all P<0.01）.  Conclusion  There are significant improvements in liver function and liver fibrosis degree in a rat model of liver cirrhosis at week 4 after the transplantation of hUC-MSC， and frozen or fresh cell preparation and different transplantation approaches have no significant influence on treatment outcome.

     

    • FullText(HTML)
  • loading
    • References(36)
  • [1]
    HERNANDEZ-GEA V, FRIEDMAN SL. Pathogenesis of liver fibrosis[J]. Annu Rev Pathol, 2011, 6: 425- 456. DOI: 10.1146/annurev-pathol-011110-130246.
    [2]
    SHAN S, ZHAO LH, MA H, et al. Definition, etiology, and epidemiology of liver cirrhosis[J]. J Clin Hepatol, 2021, 37( 1): 14- 16. DOI: 10.3969issn 1001-5256.2021.01.003.

    单姗, 赵连晖, 马红, 等. 肝硬化的定义, 病因及流行病学[J]. 临床肝胆病杂志, 2021, 37( 1): 14- 16. DOI: 10.3969issn 1001-5256.2021.01.003.
    [3]
    BAERTSCHIGER RM, SERRE-BEINIER V, MOREL P, et al. Fibrogenic potential of human multipotent mesenchymal stromal cells in injured liver[J]. PLoS One, 2009, 4( 8): e6657. DOI: 10.1371/journal.pone.0006657.
    [4]
    BARNETT R. Liver cirrhosis[J]. Lancet, 2018, 392( 10144): 275. DOI: 10.1016/S0140-6736(18)31659-3.
    [5]
    XIE RP, GU MQ, ZHANG FB, et al. Current status and prospect of surgical technique of liver transplantation[J]. Ogran Transplant, 2022, 13( 1): 105- 110. DOI: 10.3969/j.issn.1674-7445.2022.01.016.

    谢闰鹏, 谷明旗, 张凤博, 等. 肝移植手术技术的现状和展望[J]. 器官移植, 2022, 13( 1): 105- 110. DOI: 10.3969/j.issn.1674-7445.2022.01.016.
    [6]
    DING DC, SHYU WC, LIN SZ. Mesenchymal stem cells[J]. Cell Transplant, 2011, 20( 1): 5- 14. DOI: 10.3727/096368910X.
    [7]
    SHI Y, WANG Y, LI Q, et al. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases[J]. Nat Rev Nephrol, 2018, 14( 8): 493- 507. DOI: 10.1038/s41581-018-0023-5.
    [8]
    MAHMOOD A, SEETHARAMAN R, KSHATRIYA P, et al. Stem cell transplant for advanced stage liver disorders: current scenario and future prospects[J]. Curr Med Chem, 2020, 27( 37): 6276- 6293. DOI: 10.2174/0929867326666191004161802.
    [9]
    ALFAIFI M, EOM YW, NEWSOME PN, et al. Mesenchymal stromal cell therapy for liver diseases[J]. J Hepatol, 2018, 68( 6): 1272- 1285. DOI: 10.1016/j.jhep.2018.01.030.
    [10]
    XU Y, LIU P, MU YP. Liver stem cell therapy for cirrhosis: advances in cell classification and selection[J]. J Clin Hepatol, 2015, 31( 8): 1360- 1364. DOI: 10.3969/j.issn.1001-5256.2015.08.047.

    徐莹, 刘平, 慕永平. 干细胞治疗肝硬化的研究进展[J]. 临床肝胆病杂志, 2015, 31( 8): 1360- 1364. DOI: 10.3969/j.issn.1001-5256.2015.08.047.
    [11]
    LEE C, KIM M, HAN J, et al. Mesenchymal stem cells influence activation of hepatic stellate cells, and constitute a promising therapy for liver fibrosis[J]. Biomedicines, 2021, 9( 11): 1598. DOI: 10.3390/biomedicines9111598.
    [12]
    CHAI NL, ZHANG XB, CHEN SW, et al. Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats[J]. World J Gastroenterol, 2016, 22( 26): 6036- 6048. DOI: 10.3748/wjg.v22.i26.6036.
    [13]
    SO EC, WONG KL, HUANG TC, et al. Tetramethylpyrazine protects mice against thioacetamide-induced acute hepatotoxicity[J]. J Biomed Sci, 2002, 9( 5): 410- 414. DOI: 10.1007/BF02256534.
    [14]
    IDRISS NK, SAYYED HG, OSAMA A, et al. Treatment efficiency of different routes of bone marrow-derived mesenchymal stem cell injection in rat liver fibrosis model[J]. Cell Physiol Biochem, 2018, 48( 5): 2161- 2171. DOI: 10.1159/000492558.
    [15]
    TANG H, YIN YX, LIU W, et al. Effects of Xuefu Zhuyu decoction and its extracts on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet[J]. J Clin Hepatol, 2022, 38( 12): 2728- 2737. DOI: 10.3969/j.issn.1001-5256.2022.12.010.

    唐浩, 尹艺晓, 刘伟, 等. 血府逐瘀汤及其不同提取部位对高脂饮食诱导的非酒精性脂肪性肝病小鼠模型的影响[J]. 临床肝胆病杂志, 2022, 38( 12): 2728- 2737. DOI: 10.3969/j.issn.1001-5256.2022.12.010.
    [16]
    DIAO R, CHEN ZL, LYU YS, et al. Effect of entecavir combined with triple therapy on hypersplenism with esophageal varices bleeding in patients with hepatitis B cirrhosis[J]. Trauma Crit Care Med, 2022, 10( 3): 210- 212. DOI: 10.16048/j.issn.2095-5561.2022.03.14.

    刁睿, 陈治梁, 吕永双, 等. 恩替卡韦联合三联疗法治疗乙肝肝硬化脾功能亢进伴食管静脉曲张破裂出血效果研究[J]. 创伤与急危重病医学, 2022, 10( 3): 210- 212. DOI: 10.16048/j.issn.2095-5561.2022.03.14.
    [17]
    SHANG YY, XU WT, GUO XZ, et al. Progress in the application of terlipressin in the treatment of liver cirrhosis complications[J]. Clin J Med Offic, 2022, 50( 9): 884- 886. DOI: 10.16680/j.1671-3826.2022.09.02.

    商一扬, 许文涛, 郭晓钟, 等. 特利加压素在肝硬化并发症中应用研究进展[J]. 临床军医杂志, 2022, 50( 9): 884- 886. DOI: 10.16680/j.1671-3826.2022.09.02.
    [18]
    TERAI S, TAKAMI T, YAMAMOTO N, et al. Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells[J]. Tissue Eng Part B Rev, 2014, 20( 3): 206- 210. DOI: 10.1089/ten.TEB.2013.0527.
    [19]
    ZHANG GZ, SUN HC, ZHENG LB, et al. In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis[J]. World J Gastroenterol, 2017, 23( 46): 8152- 8168. DOI: 10.3748/wjg.v23.i46.8152.
    [20]
    SEO KW, SOHN SY, BHANG DH, et al. Therapeutic effects of hepatocyte growth factor-overexpressing human umbilical cord blood-derived mesenchymal stem cells on liver fibrosis in rats[J]. Cell Biol Int, 2014, 38( 1): 106- 116. DOI: 10.1002/cbin.10186.
    [21]
    MOTAWI TM, ATTA HM, SADIK NA, et al. The therapeutic effects of bone marrow-derived mesenchymal stem cells and simvastatin in a rat model of liver fibrosis[J]. Cell Biochem Biophys, 2014, 68( 1): 111- 125. DOI: 10.1007/s12013-013-9698-1.
    [22]
    de LUNA-SALDIVAR MM, MARINO-MARTINEZ IA, FRANCO-MOLINA MA, et al. Advantages of adipose tissue stem cells over CD34(+) mobilization to decrease hepatic fibrosis in Wistar rats[J]. Ann Hepatol, 2019, 18( 4): 620- 626. DOI: 10.1016/j.aohep.2018.12.005.
    [23]
    AURICH H, SGODDA M, KALTWASSER P, et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo[J]. Gut, 2009, 58( 4): 570- 581. DOI: 10.1136/gut.2008.154880.
    [24]
    SAULNIER N, PISCAGLIA AC, PUGLISI MA, et al. Molecular mechanisms underlying human adipose tissue-derived stromal cells differentiation into a hepatocyte-like phenotype[J]. Dig Liver Dis, 2010, 42( 12): 895- 901. DOI: 10.1016/j.dld.2010.04.013.
    [25]
    SONG YM, LIAN CH, WU CS, et al. Effects of bone marrow-derived mesenchymal stem cells transplanted via the portal vein or tail vein on liver injury in rats with liver cirrhosis[J]. Exp Ther Med, 2015, 9( 4): 1292- 1298. DOI: 10.3892/etm.2015.2232.
    [26]
    TSUCHIYA A, TAKEUCHI S, WATANABE T, et al. Mesenchymal stem cell therapies for liver cirrhosis: MSCs as“conducting cells” for improvement of liver fibrosis and regeneration[J]. Inflamm Regen, 2019, 39: 18. DOI: 10.1186/s41232-019-0107-z.
    [27]
    ULLAH M, LIU DD, THAKOR AS. Mesenchymal stromal cell homing: mechanisms and strategies for improvement[J]. iScience, 2019, 15: 421- 438. DOI: 10.1016/j.isci.2019.05.004.
    [28]
    HUANG S, XU L, ZHANG Y, et al. Systemic and local administration of allogeneic bone marrow-derived mesenchymal stem cells promotes fracture healing in rats[J]. Cell Transplant, 2015, 24( 12): 2643- 2655. DOI: 10.3727/096368915X687219.
    [29]
    LIESVELD JL, SHARMA N, ALJITAWI OS. Stem cell homing: From physiology to therapeutics[J]. Stem Cells, 2020, 38( 10): 1241- 1253. DOI: 10.1002/stem.3242.
    [30]
    CUI LL, NITZSCHE F, PRYAZHNIKOV E, et al. Integrin alpha4 overexpression on rat mesenchymal stem cells enhances transmigration and reduces cerebral embolism after intracarotid injection[J]. Stroke, 2017, 48( 10): 2895- 900. DOI: 10.1161/STROKEAHA.117.017809.
    [31]
    YUAN M, HU X, YAO L, et al. Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease[J]. Stem Cell Res Ther, 2022, 13( 1): 179. DOI: 10.1186/s13287-022-02858-4.
    [32]
    DAVE C, MEI S HJ, MCRAE A, et al. Comparison of freshly cultured versus cryopreserved mesenchymal stem cells in animal models of inflammation: A pre-clinical systematic review[J]. Elife, 2022, 11: e75053. DOI: 10.7554/eLife.75053.
    [33]
    CAMPARD D, LYSY PA, NAJIMI M, et al. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells[J]. Gastroenterology, 2008, 134( 3): 833- 848. DOI: 10.1053/j.gastro.2007.12.024.
    [34]
    LIU M, WANG JS, LIU MY, et al. Study of immunomodulatory function of exosomes derived from human umbilical cord mesenchymal stem cells[J]. Natl Med J China, 2015, 95( 32): 2630- 2633. DOI: 10.3760/cma.j.issn.0376-2491.2015.32.014.

    刘明, 汪劲松, 刘沐芸, 等. 人脐带间充质干细胞外泌体免疫调节功能的研究[J]. 中华医学杂志, 2015, 95( 32): 2630- 2633. DOI: 10.3760/cma.j.issn.0376-2491.2015.32.014.
    [35]
    ZHANG LT, PENG XB, FANG XQ, et al. Human umbilical cord mesenchymal stem cells inhibit proliferation of hepatic stellate cells in vitro[J]. Int J Mol Med, 2018, 41( 5): 2545- 2552. DOI: 10.3892/ijmm.2018.3500.
    [36]
    XUAN J, FENG W, AN ZT, et al. Anti-TGFbeta-1 receptor inhibitor mediates the efficacy of the human umbilical cord mesenchymal stem cells against liver fibrosis through TGFbeta-1/Smad pathway[J]. Mol Cell Biochem, 2017, 429( 1-2): 113- 122. DOI: 10.1007/s11010-017-2940-1.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)  / Tables(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (173) PDF downloads(29) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return