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      Schisandrin B promotes hepatic differentiation from human umbilical cord mesenchymal stem cells

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          Summary

          Human umbilical cord mesenchymal stem cells (UC-MSCs)-derived hepatocyte-like cells (HLCs) have shown great promise in the treatment of liver diseases. However, most current induction protocols yield hepatocyte-like cells with limited function as compared with primary hepatocytes. Schisandrin B (Sch B) is one of the main components of Schisandra chinensis, which can prevent fibrosis progression and promote liver cell regeneration. Herein, we investigated the effects of Sch B on hepatic differentiation of UC-MSCs. We found that treatment with 10 μM Sch B from the second stage of the differentiation process increased hepatic marker levels and hepatic function. Additionally, RNA-seq analysis revealed that Sch B promoted hepatic differentiation via activating the JAK2/STAT3 pathway. When transplanted HLCs into mice with CCL 4-induced liver fibrosis, Sch B-treated HLCs exhibited significant therapeutic effects. This study provides an optimized hepatic differentiation protocol for UC-MSCs based on Sch B, yielding functioning cells for liver disease treatment.

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          Highlights

          • •

            Schisandrin B enhances the hepatic differentiation and maturation of UC-MSCs

          • •

            Schisandrin B promotes hepatic differentiation via activation of JAK2/STAT3 pathway

          • •

            Schisandrin B-treated hepatocyte-like cells alleviate liver fibrosis in mice

          Abstract

          Cellular therapy; Stem cells research; Bioactive plant product

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          Most cited references53

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          Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

          M Dominici, K Le Blanc, I. Mueller … (2006)
          The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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            Burden of liver diseases in the world

            Sumeet K Asrani, Harshad Devarbhavi, John Eaton … (2019)
            Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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              The JAK-STAT pathway: impact on human disease and therapeutic intervention.

              John J. O’Shea, Daniella M. Schwartz, Alejandro Villarino … (2015)
              The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Genetic mutations and polymorphisms are functionally relevant to a variety of human diseases, especially cancer and immune-related conditions. The clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that targets JAKs.
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                Author and article information

                Contributors
                Shiyuan Xu
                Ying Zhang
                Shuqin Zhou
                Journal
                Journal ID (nlm-ta): iScience
                Journal ID (iso-abbrev): iScience
                Title: iScience
                Publisher: Elsevier
                ISSN (Electronic): 2589-0042
                Publication date PMC-release: 15 January 2024
                Publication date Collection: 16 February 2024
                Publication date (Electronic): 15 January 2024
                Volume: 27
                Issue: 2
                Electronic Location Identifier: 108912
                Affiliations
                [1 ]Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China
                [2 ]Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China
                [3 ]Department of Anesthesiology, First People’s Hospital of Kashi, Kashi 844000, China
                [4 ]General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China
                [5 ]Anesthesiology Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen 518172, China
                Author notes
                [∗ ]Corresponding author xsy998@ 123456smu.edu.cn
                [∗∗ ]Corresponding author yingzhang0831@ 123456163.com
                [∗∗∗ ]Corresponding author zhoushuqin@ 123456smu.edu.cn
                [6]

                These authors contributed equally

                [7]

                Lead contact

                Article
                Publisher Item ID: S2589-0042(24)00133-0 Publisher ID: 108912
                DOI: 10.1016/j.isci.2024.108912
                PMC ID: 10844828
                PubMed ID: 38323006
                SO-VID: a5dd79b7-ab13-4978-b7a1-97a48a9bb5d8
                Copyright © © 2024 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 6 June 2023
                Date revision received : 30 October 2023
                Date accepted : 11 January 2024
                Categories
                Subject: Article

                Keywords: cellular therapy,stem cells research,bioactive plant product
                Data availability:
                Keywords: cellular therapy, stem cells research, bioactive plant product

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