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

Meixian Jin; Xiao Yi; Xiaojuan Zhu; Wei Hu; Simin Wang; Qi Chen; Wanren Yang; Yang Li; Shao Li; Qing Peng; Mingxin Pan; Yi Gao; Shiyuan Xu; Ying Zhang; Shuqin Zhou

doi:10.1016/j.isci.2024.108912

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

iScience. 2024 Jan 15;27(2):108912. doi: 10.1016/j.isci.2024.108912. eCollection 2024 Feb 16.

Authors

Meixian Jin¹, Xiao Yi², Xiaojuan Zhu³, Wei Hu¹, Simin Wang¹, Qi Chen¹, Wanren Yang⁴, Yang Li⁴, Shao Li⁴, Qing Peng⁴, Mingxin Pan⁴, Yi Gao⁴, Shiyuan Xu¹, Ying Zhang⁴, Shuqin Zhou^{1

5}

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.

Abstract

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 CCL₄-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.

Keywords: Bioactive plant product; Cellular therapy; Stem cells research.