Advance in the study of bone marrow mesenchymal stem cell differentiation into hepatocyte in vitro

doi:10.16098/j.issn.0529-1356.2015.05.023

Abstract

Abstract:

Liver diseases have become one of the most important causes of morbidity and mortality in the world. Therapeutic methods such as orthotopic liver transplantation, hepatocyte transplantation, bioartificial liver etc are considered to treat the advanced liver disease. However, the lack of liver donor in liver transplantation and the shortage of cells sources in cytotherapy are the major obstacles for these treatment methods. Exploring new origins of extra-hepatic cells is needed. Bone marrow mesenchymal stem cells (BMSCs), characterized as multiple differentiation, rapid self-renewal, and easy to be cultured and proliferated, have been considered as the most promising source of cells. A number of recent studies have shown that BMSCs can be differentiated into hepatocytes like cells (HLCs) in vitroandin vivo. This paper reviews the up-to-date achievements and progresses in the field of isolation, characterization and induction of BMSCs, summarizes the superiority and existence question of each kind of induction condition, and finally makes a summary and expectation for this research field.

Key words: Bone marrow mesenchymal stem cell, Induction, Differentiation, Hepatocyte-like cell

DAI Ke-qiang DING Yi FAN Jin-yu XU Cun-shuan*. Advance in the study of bone marrow mesenchymal stem cell differentiation into hepatocyte in vitro[J]. AAS, 2015, 46(5): 704-709.

References

［1］Ng KK，Lo CM. Liver transplantation in Asia: past, present and future［J］. Ann Acad Med Singapore，2009，38（4）：310-322.
［2］Kim DS，Yu YD，Jung SW，et al. Balanced approach can help initial outcomes: analysis of initial 50 cases of a new liver transplantation program in East Asia［J］. Ann Surg Treat Res，2014，87（1）：22-27.
［3］Chang YM，Chung KP，Chen TW，et al. Intention of donors to re-donate livers after living donor liver transplantation in a liver transplant center in Asia［J］. Ann Transplant，2014，19(3)：421-426.
［4］Block GD， Locker J，Bowen WC，et al. Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium［J］. J Cell Biol，1996，132（6）：1133-1149.
［5］Kuo TK，Hung SP， Chuang CH，et al. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells［J］. Gastroenterology，2008，134（7）：2111-2121.
［6］Friedenstein AJ. Chailakhyan RY, Gerasimov UV. Bone marrow asteogenic stem cells: in vitro cultivation and transplantation indiffusion chambers［J］. Cell Tissue Kinet, 1987, 20(3): 263-272.
［7］Hang HL，Xia Q. Role of BMSCs in liver regeneration and metastasis after hepatectomy［J］. World J Gastroenterol，2014，20（1）：126-132.
［8］Pontikoglou C， Deschaseaux F， Sensebe L，et al. Bone marrow mesenchymal stem cells: biological properties and their role in hematopoiesis and hematopoietic stem cell transplantation［J］. Stem Cell Rev，2011，7（3）：569-589.
［9］Sreejit P，Dilip KB，Verma RS. Generation of mesenchymal stem cell lines from murine bone marrow［J］. Cell Tissue Res，2012，350（1）：55-68.
［10］Polisetti N，Chaitanya VG，Babu PP，et al. Isolation, characterization and differentiation potential of rat bone marrow stromal cells［J］. Neurol India，2010，58（2）：201-208.
［11］Kern S，Eichler H，Stoeve J，et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue［J］. Stem Cells，2006，24（5）：1294-1301.
［12］Hasebe Y，Hasegawa S，Hashimoto N，et al. Analysis of cell characterization using cell surface markers in the dermis［J］. J Dermatol Sci，2011，62（2）：98-106.
［13］Petersen BE，Bowen WC，Patrene KD，et al. Bone marrow as a potential source of hepatic oval cells［J］. Science，1999，284（5417）：1168-1170.
［14］Duncan SA. Mechanisms controlling early development of the liver［J］. Mech Dev，2003，120（1）：19-33.
［15］Lagasse E，Connors H，Al-Dhalimy M，et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo［J］. Nat Med，2000，6（11）：1229-1234.
［16］Zhu BB，Cai XH, Sun YP. Induction effect of hepatocyte growth factor and insulin-like growth factor on cardiac stem cells［J］. Acta Anatomica Sinica, 2014，45（5）：663-669. (in Chinese)
朱蓓蓓，蔡新华，孙银平. 肝细胞生长因子和类胰岛素样生长因子对心肌干细胞的诱导作用［J］. 解剖学报，2014，45（5）：663-669.
［17］Wang PP，Wang JH，Yan ZP，et al. Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF induction［J］. Biochem Biophys Res Commun，2004，320（3）：712-716.
［18］Saji Y，Tamura S，Yoshida Y，et al. Basic fibroblast growth factor promotes the trans-differentiation of mouse bone marrow cells into hepatic lineage cells via multiple liver-enriched transcription factors［J］. J Hepatol，2004，41（4）：545-550.
［19］Akino K，Mineta T，Fukui M，et al. Bone morphogenetic protein-2 regulates proliferation of human mesenchymal stem cells［J］. Wound Repair Regen，2003，11（5）：354-360.
［20］Ishikawa T，Terai S，Urata Y，et al. Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice［J］. Cell Tissue Res，2007，327（3）：463-470.
［21］Hu J, Mu L,Luo EJ. Induced differentiation ofBM-MSCs into hepatocyte-like cells in vitro［J］. Journal of Microbiology, 2008，28(3)：30-33. (in Chinese)
胡晶, 牟玲, 罗恩杰. 体外诱导骨髓间充质干细胞向肝细胞样细胞方向分化［J］. 微生物学杂志，2008，28(3)：30-33.
［22］Kang XQ，Zang WJ， Song TS，et al. Rat bone marrow mesenchymal stem cells differentiate into hepatocytes in vitro［J］. World J Gastroenterol，2005，11（22）：3479-3484.
［23］Luo W, Xiao EH, Luo JG. et al. In vitro combination of different-concentration hepatocyte growth factor and epidermal growth factor induces differentiation of rabbit bone marrow mesenchymal stem cells into hepatocytes［J］.Journal of Clinical Rehabilitative Tissue Engineering Research，2011，15（36）：6727-6731. (in Chinese)
罗伟，肖恩华，罗建光,等.不同浓度肝细胞生长因子及表皮细胞生长因子体外联合诱导兔骨髓间充质干细胞向肝细胞分化［J］. 中国组织工程研究与临床康复，2011，15（36）：6727-6731.
［24］Lee KD， Kuo TK， WhangPeng J，et al. In vitro hepatic differentiation of human mesenchymal stem cells［J］. Hepatology，2004，40（6）：1275-1284.
［25］Wang ZhQ, Li ChP, Du GH, et al. Several kinds of cytokines induce differentiation of bone marrow mesenchymal stem cells into hepatocytes［J］. Journal of Clinical Rehabilitative Tissue Engineering Research，2008，12（21）：4035-4038. (in Chinese)
王忠琼，李昌平，杜光红，等. 多种细胞因子诱导骨髓间充质干细胞向肝细胞的分化［J］. 中国组织工程研究与临床康复，2008，12（21）：4035-4038.
［26］Ju S，Teng GJ，Lu H，et al. In vivo MR tracking of mesenchymal stem cells in rat liver after intrasplenic transplantation［J］. Radiology，2007，245（1）：206-215.
［27］Abdel-Aziz MT, Atta HM， Mahfouz S，et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis［J］. Clin Biochem，2007，40（12）：893-899.
［28］Zhang ShQ，Fan QJ，Zhao WJ, et al. Study of hepatopathy patient serum inducing mesenchymal stem cell expressing hepatocyte marker［J］. Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases，2006，16（4）：229-234. (in Chinese)
张淑芹, 范庆杰，赵文静，等. 肝病患者血清诱导间充质干细胞表达肝细胞特异性标志物的实验研究［J］. 中西医结合肝病杂志，2006，16（4）：229-234.
［29］Hong H，Chen JZ，Zhou F，et al. Influence of serum from liver-damaged rats on differentiation tendency of bone marrow-derived stem cells［J］. World J Gastroenterol，2004，10（15）：2250-2253.
［30］Yu Y，Yao AH， Chen N，et al. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration［J］. Mol Ther，2007，15（7）：1382-1389.
［31］Lange C， Bassler P， Lioznov MV，et al. Hepatocytic gene expression in cultured rat mesenchymal stem cells［J］. Transplant Proc，2005，37（1）：276-279.
［32］Okumoto K， Saito T， Haga H，et al. Characteristics of rat bone marrow cells differentiated into a liver cell lineage and dynamics of the transplanted cells in the injured liver［J］. J Gastroenterol，2006，41（1）：62-69.
［33］Lange C， Bruns H， Kluth D，et al. Hepatocytic differentiation of mesenchymal stem cells in cocultures with fetal liver cells［J］. World J Gastroenterol，2006，12（15）：2394-2397.
［34］Kazemnejad S，Allameh A，Soleimani M，et al. Biochemical and molecular characterization of hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel three-dimensional biocompatible nanofibrous scaffold［J］. J Gastroenterol Hepatol，2009，24（2）：278-287.
［35］Piryaei A，Valojerdi MR，Shahsavani M，et al. Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells on nanofibers and their transplantation into a carbon tetrachloride-induced liver fibrosis model［J］. Stem Cell Rev，2011，7（1）：103-118.
［36］Lin N， Lin J，Bo L，et al. Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells in an alginate scaffold［J］. Cell Prolif，2010，43（5）：427-434.
［37］Sekiya S， Suzuki A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors［J］. Nature，2011，475（7356）：390-393.
［38］Huang P， He Z， Ji S，et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors［J］. Nature，2011，475（7356）：386-389.
［39］Yu B，He ZY，You P，et al. Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors［J］. Cell Stem Cell，2013，13（3）：328-340.
［40］Sekioya S, Suzuki A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors［J］. Nature, 2011, 475(7356):390-393.
［41］Dai K，Chen R, Ding Y, et al. Induction of functional hepatocyte-like cells by overexpression of FOXA3 and HNF4 in rat bone marrow mesenchymal stem Cells［J］. Cells Tissues Organs, 2014, 200(2): 132-140.

[1]	XIE Hui-lan FANG Fang LIN Yi. Mechanism of Chir99021 regulating Wnt/β-catenin signaling pathway inhibiting osteogenic differentiation of rat dental pulp stem cells [J]. Acta Anatomica Sinica, 2024, 55(1): 67-72.
[2]	JI Rui-jie LI Wen JIN Guo-hua ZHANG Xin-hua. Expression and effect of roundabout guidance receptor 1 during valproate induced neural stem cells differentiation [J]. Acta Anatomica Sinica, 2023, 54(3): 255-260.
[3]	XIE Qiu-min SUN Yan-ting XU Hao LIU Hui-wen YI Qin TAN Bin TIAN Jie ZHU Jing. Glucose and serum deprivation under hypoxia treatment inducing oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells through inhibition of Nrf2 signaling pathway [J]. Acta Anatomica Sinica, 2023, 54(3): 305-312.
[4]	LI Guang LI Jie ZHANG Ping . Mechanism of microRNA-30d-5p regulating osteogenic differentiation of bone marrow stromal cells through glucose-regulated 78 [J]. Acta Anatomica Sinica, 2023, 54(2): 195-201.
[5]	ZHANG Ya-qun FU Li REN Yi-yan QIAO Yan-zi ZHAO Dong-mei. Isolation and culture of rat adipose-derived stem cells and differentiation into oligodendrocyte precursor cells [J]. Acta Anatomica Sinica, 2022, 53(5): 557-562.
[6]	QIN Yang-yang XU Long-fei WANG Qi HAN Jing HONG Yan. Effect of exosomes derived from bone marrow mesenchymal stem cells on the polarization of mouse liver Kupffer cells [J]. Acta Anatomica Sinica, 2022, 53(4): 447-452.
[7]	ZHOU Hong KANG Quan XIE Sheng-nan CHEN Jie SHI Yu-lu LUO Qing. Reversing malignant biological behavior of osteosarcoma by knocking down 3-phosphoglycerin dehydrogenase targeting energy metabolism [J]. Acta Anatomica Sinica, 2022, 53(4): 488-497.
[8]	SONG Hui-fang TAN Jia-yin LIU Yang ZHANG Wei-guo GUO Rui. Hypoxic pretreatment enhancing the angiogenesis of aged human bone marrow mesenchymal stem cells through hypoxia inducible factor-1α [J]. Acta Anatomica Sinica, 2022, 53(1): 35-41.
[9]	LI Yong-tao JIANG Yang SUN Shi-zhu WANG Lu-lu LIU Dang-yang LIU Na ZHANG Xiao-dong SHEN Lei. Exploring the effect of C-X-C motif chemokine ligand-13 on the proliferation and migration of mesenchymal stem cells based on network pharmacology [J]. Acta Anatomica Sinica, 2021, 52(6): 889-900.
[10]	WANG Shanshan LI Wen HE Hui QIN Jian-bing TIAN Mei-ling ZHAO He-yan CHENG Xiang JIN Guo-hua. Expression and role of Huntingtin-associated protein 1 during valproate induced neural stem cells differentiation [J]. Acta Anatomica Sinica, 2021, 52(2): 182-188.
[11]	JU Xiao-jun NIU You-ya RAO Li-bing YI Li-ming XIANG Sha ZHANG Ying-jun. Experiment of the differentiation of adipose-derived stem cells into fibroblasts [J]. Acta Anatomica Sinica, 2020, 51(4): 513-519.
[12]	LI Jiao Lü Yang LIU Yang WANG Hao-yu ZHAO Ya-ru WANG Xue-jiao WANG Hai-ping. Role of fibroblast growth factor 2 and tanshinoneⅡA in the differentiation of rat bone marrow mesenchymal stem cells into cardiomyocyte-like cells [J]. Acta Anatomica Sinica, 2020, 51(4): 520-527.
[13]	DU Bao-pu DU Jing. Analysis of physique types and their causes of modern Chinese population by head-to-face measurements [J]. Acta Anatomica Sinica, 2019, 50(6): 805-815.
[14]	LI Xiu-quan BAI Shu-ling AO Qiang WANG Xiao-hong CHANG Shi-jie TIAN Xiao-hong TONG Hao FAN Jun. Effects of Klotho on the proliferation and differentiation of rat bone marrow mesenchymal stem cells [J]. Acta Anatomica Sinica, 2019, 50(6): 729-734.
[15]	LIU Yang Lü Yang WANG Hao-yu LI Jiao REN Jun-xu WANG Hai-ping. Optimal concentration of 1,25-vitamin-D₃ to induce the differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells in vitro [J]. Acta Anatomica Sinica, 2019, 50(5): 580-588.