Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Sodium Butyrate Pre-Treatment Enhance Differentiation of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) into Hepatocytes and Improve Liver Injury

Author(s): Qiu-Yun Li, Juan Chen, Yong-Heng Luo, Wei Zhang and En-Hua Xiao*

Volume 22, Issue 7, 2022

Published on: 06 January, 2022

Page: [663 - 674] Pages: 12

DOI: 10.2174/1566524021666211014161716

Price: $65

Abstract

Objective: The treatment of liver failure by stem cell transplantation has attracted growing interest. Herein, we aim to explore the role of sodium butyrate (NaB) in the hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro and vivo.

Materials & Methods: We isolated BM-MSCs from the mononuclear cell fraction of rabbit bone marrow samples and identified the cells by Immunophenotypic analysis. We investigated the effects of different concentrations and induction conditions. The histone deacetylase inhibitor NaB induced hepatic differentiation of BM-MSCs under liverspecific factors induction in vitro. Morphological features, liver-specific gene and protein expression, and functional analyses in vitro and vivo were performed to evaluate the hepatic differentiation of BM-MSCs.

Results: Our results showed that pre-treated NaB inhibited the expression of the liverspecific protein in a dose-dependent manner. The induction efficiency of NaB with 24h pre-treatment was higher than that of NaB continuous intervention. 0.5 mM 24h NaB pre-treated cells can improve liver tissue damage in vivo. The liver ALB, AAT, and the serum TP were significantly increased, while the serum ALT was significantly reduced.

Conclusion: Continuous NaB treatment can inhibit BM-MSCs proliferation in a dosedependent manner at a certain concentration range. 0.5 mM 24h pre-treatment of NaB enhanced differentiation of BM-MSCs into hepatocytes and improved liver injury in vitro and vivo.

Keywords: Bone marrow mesenchymal stem cells, Sodium butyrate, Hepatic differentiation, liver injury, in vitro, in vivo.

« Previous
[1]
Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418(6893): 41-9.
[http://dx.doi.org/10.1038/nature00870] [PMID: 12077603]
[2]
Lee HS, Huang GT, Chiang H, et al. Multipotential mesenchymal stem cells from femoral bone marrow near the site of osteonecrosis. Stem Cells 2003; 21(2): 190-9.
[http://dx.doi.org/10.1634/stemcells.21-2-190] [PMID: 12634415]
[3]
Fisher M, Hyzy S, Guldberg RE, Schwartz Z, Boyan BD. Regeneration of bone marrow after tibial ablation in immunocompromised rats is age dependent. Bone 2010; 46(2): 396-401.
[http://dx.doi.org/10.1016/j.bone.2009.09.029] [PMID: 19800046]
[4]
Quintavalla J, Uziel-Fusi S, Yin J, et al. Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects. Biomaterials 2002; 23(1): 109-19.
[http://dx.doi.org/10.1016/S0142-9612(01)00086-2] [PMID: 11762829]
[5]
Van Damme A, Vanden Driessche T, Collen D, Chuah MK. Bone marrow stromal cells as targets for gene therapy. Curr Gene Ther 2002; 2(2): 195-209.
[http://dx.doi.org/10.2174/1566523024605645] [PMID: 12109216]
[6]
De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A, et al. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 2012; 12(5): 574-91.
[http://dx.doi.org/10.2174/156652412800619950] [PMID: 22515979]
[7]
Hamazaki T, Iiboshi Y, Oka M, et al. Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Lett 2001; 497(1): 15-9.
[http://dx.doi.org/10.1016/S0014-5793(01)02423-1] [PMID: 11376655]
[8]
Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429(6990): 457-63.
[http://dx.doi.org/10.1038/nature02625] [PMID: 15164071]
[9]
Johnson D, Walmsley R. Histone-deacetylase inhibitors produce positive results in the GADD45a-GFP GreenScreen HC assay. Mutat Res 2013; 751(2): 96-100.
[http://dx.doi.org/10.1016/j.mrgentox.2012.12.009] [PMID: 23340162]
[10]
Chen J, Li Q-Y, Luo Y-H, Xiao E-H. Continuous zebularine treatment enhances hepatic differentiation of mesenchymal stem cells under liver-specific factors induction in vitro. Life Sci 2018; 215: 57-63.
[http://dx.doi.org/10.1016/j.lfs.2018.10.049] [PMID: 30473025]
[11]
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 2006; 8(4): 315-7.
[http://dx.doi.org/10.1080/14653240600855905] [PMID: 16923606]
[12]
Rambhatla L, Chiu C-P, Kundu P, Peng Y, Carpenter MK. Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplant 2003; 12(1): 1-11.
[http://dx.doi.org/10.3727/000000003783985179] [PMID: 12693659]
[13]
Cao J, Shang CZ, Lü LH, et al. Differentiation of embryonic stem cells into hepatocytes that coexpress coagulation factors VIII and IX. Acta Pharmacol Sin 2010; 31(11): 1478-86.
[http://dx.doi.org/10.1038/aps.2010.100] [PMID: 20953206]
[14]
Liu J, Wang Y, Wu Y, Ni B, Liang Z. Sodium butyrate promotes the differentiation of rat bone marrow mesenchymal stem cells to smooth muscle cells through histone acetylation. PLoS One 2014; 9(12)e116183
[http://dx.doi.org/10.1371/journal.pone.0116183] [PMID: 25548915]
[15]
Xie C, Wu B, Chen B, et al. Histone deacetylase inhibitor sodium butyrate suppresses proliferation and promotes apoptosis in osteosarcoma cells by regulation of the MDM2-p53 signaling. OncoTargets Ther 2016; 9: 4005-13.
[http://dx.doi.org/10.2147/OTT.S105418] [PMID: 27445491]
[16]
Nakagawa H, Sasagawa S, Itoh K. Sodium butyrate induces senescence and inhibits the invasiveness of glioblastoma cells. Oncol Lett 2018; 15(2): 1495-502.
[PMID: 29434841]
[17]
Bogacheva MS, Khan S, Kanninen LK, Yliperttula M, Leung AW, Lou YR. Differences in definitive endoderm induction approaches using growth factors and small molecules. J Cell Physiol 2018; 233(4): 3578-89.
[http://dx.doi.org/10.1002/jcp.26214] [PMID: 29044512]
[18]
Mali P, Chou BK, Yen J, et al. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells 2010; 28(4): 713-20.
[http://dx.doi.org/10.1002/stem.402] [PMID: 20201064]
[19]
Naeem N, Haneef K, Kabir N, Iqbal H, Jamall S, Salim A. DNA methylation inhibitors, 5-azacytidine and zebularine potentiate the transdifferentiation of rat bone marrow mesenchymal stem cells into cardiomyocytes. Cardiovasc Ther 2013; 31(4): 201-9.
[http://dx.doi.org/10.1111/j.1755-5922.2012.00320.x] [PMID: 22954287]
[20]
Li W, Yu M, Luo S, et al. DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate. J Nutr Biochem 2013; 24(7): 1295-301.
[http://dx.doi.org/10.1016/j.jnutbio.2012.11.001] [PMID: 23332600]
[21]
Horrillo A, Pezzolla D, Fraga MF, et al. Zebularine regulates early stages of mESC differentiation: effect on cardiac commitment. Cell Death Dis 2013; 4: e570-0.
[http://dx.doi.org/10.1038/cddis.2013.88] [PMID: 23559004]
[22]
Woo DH, Kim SK, Lim HJ, et al. Direct and indirect contribution of human embryonic stem cell-derived hepatocyte-like cells to liver repair in mice. Gastroenterology 2012; 142(3): 602-11.
[http://dx.doi.org/10.1053/j.gastro.2011.11.030] [PMID: 22138358]
[23]
Lu HH, Teng GJ, Ju SH, Sun JH, Li AM, Zhang AF. Committed differentiation of transplanted bone derived mesenchymal stem cells and their potential to amend damaged liver functions: in vivo experiment with mice. Zhonghua Yi Xue Za Zhi 2007; 87(4): 223-7.
[PMID: 17425863]
[24]
Chen Y, Pan RL, Zhang XL, et al. Induction of hepatic differentiation of mouse bone marrow stromal stem cells by the histone deacetylase inhibitor VPA. J Cell Mol Med 2009; 13(8B): 2582-92.
[http://dx.doi.org/10.1111/j.1582-4934.2008.00471.x] [PMID: 18705698]
[25]
Wang B, Li W, Dean D, Mishra MK, Wekesa KS. Enhanced hepatogenic differentiation of bone marrow derived mesenchymal stem cells on liver ECM hydrogel. J Biomed Mater Res A 2018; 106(3): 829-38.
[http://dx.doi.org/10.1002/jbm.a.36278] [PMID: 29067792]
[26]
Ma HC, Shi XL, Ren HZ, Yuan XW, Ding YT. Targeted migration of mesenchymal stem cells modified with CXCR4 to acute failing liver improves liver regeneration. World J Gastroenterol 2014; 20(40): 14884-94.
[http://dx.doi.org/10.3748/wjg.v20.i40.14884] [PMID: 25356048]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy