Search JIM Advanced Search

Journal of Integrative Medicine ›› 2014, Vol. 12 ›› Issue (3): 147-155.doi: 10.1016/S2095-4964(14)60022-4

• Review • Previous Articles     Next Articles

Advances in mesenchymal stem cells combined with traditional Chinese medicine therapy for liver fibrosis

Shu Dong, Shi-bing Su   

  1. Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2013-12-18 Accepted:2014-02-28 Online:2014-05-10 Published:2014-05-15

Liver fibrosis is a primary cause of liver cirrhosis, and even hepatocarcinoma. Recently, the usage of mesenchymal stem cells (MSCs) has been investigated to improve liver fibrosis. It has been reported that the differentiation, proliferation and migration of MSCs can be regulated by traditional Chinese medicine treatment; however, the mechanisms are still unclear. In this article, the authors review the characteristics of MSCs such as multidirectional differentiation and homing, and its application in animal experiments and clinical trials. The authors also list areas that need further investigation, and look at the future prospects of clinical application of MSCs.

Key words: Mesenchymal stem cells, Liver fibrosis, Liver cirrhosis, Medicine, Chinese traditional, Therapy, Reviews

Figure 1

Literature summary of TCM on MSCs researchA: Trend of TCM research on MSCs. B: Main aspects of TCM research on MSCs. The publications on MSCs study in PubMed databases from 2004 to November, 2013. All results were screened manually with the MeSH terms “marrow mesenchymal stem cells” combined with “traditional Chinese medicine”. MSCs: marrow mesenchymal stem cells; TCM: traditional Chinese medicine."

Figure 2

Main mechanisms of cell therapy with MSCs MSCs are induced to differentiate into hepatocytes under the mediation of HGF and other cytokines. Then, MSCs migrate to sites of injured liver tissue and repair liver fibrosis through several different pathways. MSCs: mesenchymal stem cells; HGF: hepatocyte growth factor; FGF4: fibroblast growth factor 4; EGF: epidermal growth factor; OSM: oncostatin M; AFGF: acidic fibroblast growth factor; VCAM-1: vascular cell adhesion molecule-1; MMP: matrix metalloproteinase; HSCs: hepatic stellate cells."

[1] Iredale JP . Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ[J]. J Clin Invest, 2007,117(3):539-548
doi: 10.1172/JCI30542
[2] Ishikawa T, Banas A, Hagiwara K, Iwaguro H, Ochiya T . Stem cells for hepatic regeneration: the role of adipose tissue derived mesenchymal stem cells[J]. Curr Stem Cell Res Ther, 2010,5(2):182-189
doi: 10.2174/157488810791268636
[3] Parveen N, Aleem AK, Habeeb MA, Habibullah CM . An update on hepatic stem cells: bench to bedside[J]. Curr Pharm Biotechnol, 2011,12(2):226-230
doi: 10.2174/138920111794295765
[4] Zhao Q, Ren H, Zhu D, Han Z . Stem/progenitor cells in liver injury repair and regeneration[J]. Biol Cell, 2009,101(10):557-571
[5] Sobaniec-Lotowska ME, Lotowska JM, Lebensztejn DM . Ultrastructure of oval cells in children with chronic hepatitis B, with special emphasis on the stage of liver fibrosis: the first pediatric study[J]. World J Gastroenterol, 2007,13(21):2918-2922
doi: 10.3748/wjg.v13.i21.2918
[6] Sundback CA, Vacanti JP . Alternatives to liver transplantation: from hepatocyte transplantation to tissue-engineered organs[J]. Gastroenterology, 2000,118(2):438-442
[7] Taléns-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gómez-Lechón MJ . Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells[J]. World J Gastroenterol, 2006,12(36):5834-5845
doi: 10.3748/wjg.v12.i36.5834
[8] Tatiana K, David AB . The phenotypic fate and functional role for bone marrow-derived stem cells in liver fibrosis[J]. J Hepatol, 2012,56(4):965-972
doi: 10.1016/j.jhep.2011.09.021
[9] Zheng JH, Li YH, Yuan ZK . The prospect and strategy of effect traditional Chinese medicine on bone marrow mesenchymal stem cells[J]. Liaoning Zhong Yi Yao Da Xue Xue Bao, 2009,11(5):35-37
[10] Zhao W, Li JJ, Li X, Zhang LY, He Y, Yue SQ, Wang DS, Dou KF . Intravenous injection of mesenchymal stem cells is effective in treating liver fibrosis[J]. World J Gastroenterol, 2012,18(10):1048-1058
doi: 10.3748/wjg.v18.i10.1048
[11] Cao HJ, Lin BL . Progress in application of bone marrow mesenchymal stem cells in liver fibrosis[J]. Xin Yi Xue, 2011,42(1):57-60
[12] Sun JH, Xian SX, Huang XW, Yang ZQ . Research progress in traditional Chinese medicine-induced bone marrow mesenchymal stem cell differentiation into myocardial cells in vitro[J]. Zhong Yao Xin Yao Yu Lin Chuang Yao Li, 2012,23(1):115-118
[13] Lin H, Xu R, Zhang Z, Chen L, Shi M, Wang FS . Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases[J]. Cell Mol Immunol, 2011,8(1):19-22
doi: 10.1038/cmi.2010.57
[14] Liu G, Gao M . Review of mesenchymal stem cells differentiating into hepatocytes[J]. Guo Ji Xiao Hua Bing Za Zhi, 2007,27(1):7-9
[15] Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP . Bone marrow as a potential source of hepatic oval cells[J]. Science, 1999,284(5417):1168-1170
doi: 10.1126/science.284.5417.1168
[16] Hu GH, Shen LG . Progress in research of treatment of liver fibrosis with mesenchymal stem cells[J]. Shi Jie Hua Ren Xiao Hua Za Zhi, 2007,15(34):3587-3591
[17] Shi LJ, Li SX, Sun B, Wang JH, Li HL, Jin LH . Effects of bone marrow mesenchymal stem cells on the proliferation of hepatocytes and cirrhotic fat-storing cells in vitro[J]. Zhonghua Gan Zang Bing Za Zhi, 2007,15(9):681-684
[18] Liang F, Wang YF, Yue HM, Nan X, Shi SS, Yan F, Li R, Pei XT . In vitro differentiation of human bone marrow derived mesenchymal stem cells into hepatocytes[J]. Jun Yi Jin Xiu Xue Yuan Xue Bao, 2006,27(3):230-232
[19] Kang XQ, Zang WJ, Song TS, Xu XL, Yu XJ, Li DL, Meng KW, Wu SL, Zhao ZY . Rat bone marrow mesenchymal stem cells differentiate into hepatocytes in vitro[J]. World J Gastroenterol, 2005,11(22):3479-3484
doi: 10.3748/wjg.v11.i22.3479
[20] Lu XH, Ma Li, Liu P . Induced differentiation of rat bone marrow mesenchymal stem cells into hepatocytes in vitro[J]. Zhongguo Yi Ke Da Xue Xue Bao, 2007,36(3):256-258
[21] He ZJ, Fang CH, Ma JX, Yang LP . Rat mesenchymal stem cells differentiate into hepatocyte-like cells induced by hepatocyte growth factor plus epidermal growth factor in vitro[J]. Jie Fang Jun Yi Xue Za Zhi, 2006,31(5):446-449
[22] Zhong XL, Li CP, Hu L, Wan JY . Hepatocytic differentiation of bone marrow-derived mesenchymal srem cells[J]. Shi Jie Hua Ren Xiao Hua Za Zhi, 2007,15(6):568-573
[23] Wang ZQ, Li CP, Du GH, Zhong XL, Chen X . Several kinds of cytokines induce differentiation of bone marrow mesenchymal stem cells into hepatocytes[J]. Zhongguo Zu Zhi Gong Cheng Yan Jiu Yu Lin Chuang Kang Fu, 2008,12(21):4035-4038
[24] Liu HJ, Duan HF, Lu ZZ, Wang H, Zhang QW, Wu ZZ, Wang LS . Influence of hepatocyte growth factor on biological characteristics of bone marrow-derived mesenchymal stem cells[J]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2005,13(6):1044-1048
[25] Wang LY, Xu H, Dong SW, Su YP, Pang XL, Liu DQ, Wang JP, Ran XZ . Study on transdifferentiation of allotype BMSCs into hepatocytes in mice[J]. Wei Chang Bing Xue He Gan Bing Xue Za Zhi, 2008,117(1):27-29
[26] Wu XZ, Zhao LS, Xu Q, Zhang Y, Tang H . Differentiation of bone marrow mesenchymal stem cells into hepatocytes in hepatectomized mouse[J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2005,22(6):1234-1237
[27] Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y, Shi Y . Concise review: mesenchymal stem cells and translational medicine: emerging issues[J]. Stem Cells Transl Med, 2012,1(1):51-58
doi: 10.5966/sctm.2011-0019
[28] Garcia MG, Bayo J, Bolontrade MF, Sganga L, Malvicini M, Alaniz L, Aquino JB, Fiore E, Rizzo MM, Rodriguez A, Lorenti A, Andriani O, Podhajcer O, Mazzolini G . Hepatocellular carcinoma cells and their fibrotic microenvironment modulate bone marrow-derived mesenchymal stromal cell migration in vitro and in vivo[J]. Mol Pharm, 2011,8(5):1538-1548
doi: 10.1021/mp200137c
[29] Chen N, Yu Y, Li J, Zhang LL, Liu Y, Han YP . A study on the homing capacity of bone mesenchymal stem cells to rat with acute hepatic failure[J]. Nanjing Yi Ke Da Xue Xue Bao Zi Ran Ke Xue Ban, 2007,27(7):684-688
[30] Ding DF, Li XF, Xu H, Wang Z, Liang QQ, Li CG, Wang YJ . Mechanism of resveratrol on the promotion of induced pluripotent stem cells[J]. J Integr Med, 2013,11(6):389-396
doi: 10.3736/jintegrmed2013039
[31] Cho JW, Lee CY, Ko Y . Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues[J]. J Gastroenterol Hepatol, 2012,27(8):1362-1370
doi: 10.1111/jgh.2012.27.issue-8
[32] Aldridge V, Garg A, Davies N, Bartlett DC, Youster J, Beard H, Kavanagh DP, Kalia N, Frampton J, Lalor PF, Newsome PN . Human mesenchymal stem cells are recruited to injured liver in a β1-integrin and CD44 dependent manner[J]. Hepatology, 2012,56(3):1063-1073
[33] Li C, Kong Y, Wang H, Wang S, Yu H, Liu X, Yang L, Jiang X, Li L, Li L . Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis[J]. J Hepatol, 2009,50(6):1174-1183
doi: 10.1016/j.jhep.2009.01.028
[34] Pei QW, Song XL, Yang Y, Sun ZC, Han T . Homing of BMSCs and intervention strategies of TCM[J]. Liaoning Zhong Yi Za Zhi, 2013,40(4):628-629
[35] Zhou B, Shan H, Li D, Jiang ZB, Qian JS, Zhu KS, Huang MS, Meng XC . MR tracking of magnetically labeled mesenchymal stem cells in rats with liver fibrosis[J]. Magn Reson Imaging, 2010,28(3):394-399
doi: 10.1016/j.mri.2009.12.005
[36] Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K, Abdolahzadeh L, Saghari M, Malekzadeh R . In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis[J]. Nucl Med Biol, 2011,38(7):961-967
doi: 10.1016/j.nucmedbio.2011.03.008
[37] Hwang S, Hong HN, Kim HS, Park SR, Won YJ, Choi D, Lee SG . Hepatogenic differentiation of mesenchymal stem cells in a rat model of thioacetamide-induced liver cirrhosis[J]. Cell Biol, 2012,36:279-288
[38] Oyagi S, Hirose M, Kojima M, Okuyama M, Kawase M, Nakamura T, Ohgushi H, Yagi K . Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats[J]. J Hepatol, 2006,44(4):742-748
doi: 10.1016/j.jhep.2005.10.026
[39] Mohsin S, Shams S, Ali Nasir G, Khan M, Javaid AS, Khan SN, Riazuddin S . Enhanced hepatic differentiation of mesenchymal stem cells after pretreatment with injured liver tissue[J]. Differentiation, 2011,81(1):42-48
doi: 10.1016/j.diff.2010.08.005
[40] Chang YJ, Liu JW, Lin PC, Sun LY, Peng CW, Luo GH, Chen TM, Lee RP, Lin SZ, Harn HJ, Chiou TW . Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis[J]. Life Sci, 2009,85(13-14):517-525
doi: 10.1016/j.lfs.2009.08.003
[41] Yu Y, Lu L, Qian X, Chen N, Yao A, Pu L, Zhang F, Li X, Kong L, Sun B, Wang X . Antifibrotic effect of hepatocyte growth factor-expressing mesenchymal stem cells in small-for-size liver transplant rats[J]. Stem Cells Dev, 2010,19(6):903-914
doi: 10.1089/scd.2009.0254
[42] Ezquer M, Ezquer F, Ricca M, Allers C, Conget P . Intravenous administration of multipotent stromal cells prevents the onset of non-alcoholic steatohepatitis in obese mice with metabolic syndrome[J]. J Hepatol, 2011,55(5):1112-1120
doi: 10.1016/j.jhep.2011.02.020
[43] Xu H, Qian H, Zhu W, Zhang X, Yan Y, Mao F, Wang M, Xu H, Xu W . Mesenchymal stem cells relieve fibrosis of Schistosoma japonicum-induced mouse liver injury[J]. Exp Biol Med (Maywood), 2012,237(5):585-592
doi: 10.1258/ebm.2012.011362
[44] Liu F, Chen SH, Liu QB, Fan XJ, Tang F, Zhao GQ . Reconstruction of hepatic functions after bone marrow mesenchymal stem cells transplantation[J]. Zhongguo Zu Zhi Gong Cheng Yan Jiu Yu Lin Chuang Kang Fu, 2011,15(10):1803-1808
[45] Ali G, Mohsin S, Khan M, Nasir GA, Shams S, Khan SN, Riazuddin S . Nitric oxide augments mesenchymal stem cell ability to repair liver fibrosis[J]. J Transl Med, 2012,10:75
doi: 10.1186/1479-5876-10-75
[46] Piryaei A, Valojerdi MR, Shahsavani M, Baharvand H . 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):103-108
doi: 10.1007/s12015-010-9126-5
[47] Kim S, Kim HS, Lee E, Kim HO . In vivo hepatic differentiation potential of human cord blood-derived mesenchymal stem cells[J]. Int J Mol Med, 2011,27(5):701-706
[48] Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Wang M, Zhou Y, Zhu W, Li W, Xu W . Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis[J]. Stem Cells Dev, 2013,22(6):845-854
doi: 10.1089/scd.2012.0395
[49] Aquino JB, Bolontrade MF, García MG, Podhajcer OL, Mazzolini G . Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma[J]. Gene Ther, 2010,17(6):692-708
doi: 10.1038/gt.2010.10
[50] Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M, Bagheri M, Bashtar M, Ghanaati H, Baharvand H, Ghavamzadeh A, Malekzadeh R . Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis[J]. Arch Iranian Med, 2007,10(4):459-466
[51] El-Ansary M, Abdel-Aziz I, Mogawer S, Abdel-Hamid S, Hammam O, Teaema S, Wahdan M . Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis[J]. Stem Cell Rev, 2012,8(3):972-981
doi: 10.1007/s12015-011-9322-y
[52] He JQ, Pan XN, Wang CG, Yang WL, Xiong ML, Tu MH, Xiong ZQ, Yang LL . Autologous bone marrow mesenchymal stem cells transplantation for end-stage liver disease in 39 patients[J]. Zhongguo Zu Zhi Gong Cheng Yan Jiu Yu Lin Chuang Kang Fu, 2010,14(45):8521-8525
[53] Kharaziha P , Hellstr?m PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M.Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial[J]. Eur J Gastroenterol Hepatol, 2009,21(10):1199-1205
doi: 10.1097/MEG.0b013e32832a1f6c
[54] Zhong YS, Lin N, Deng MH, Zhang FC, Tang ZF, Xu RY . Deficient proliferation of bone marrow-derived mesenchymal stem cells in patients with chronic hepatitis B viral infections and cirrhosis of the liver[J]. Dig Dis Sci, 2010,55(2):438-445
doi: 10.1007/s10620-009-0733-4
[55] Zhang GQ, Fang CH, Chi DZ . Hepatocyte growth factor induces differentiation of adult rat mesenchymal stem cells into a hepatocyte lineage in vitro[J]. Zhonghua Wai Ke Za Zhi, 2005,43(11):716-720
[56] Jung KH, Uhm YK, Lim YJ, Yim SV . Human umbilical cord blood-derived mesenchymal stem cells improve glucose homeostasis in rats with liver cirrhosis[J]. Int J Oncol, 2011,39(1):137-143
[57] Chen S, Xu L, Lin N, Pan W, Hu K, Xu R . Activation of Notch1 signaling by marrow-derived mesenchymal stem cells through cell-cell contact inhibits proliferation of hepatic stellate cells[J]. Life Sci, 2011,89(25):975-981
doi: 10.1016/j.lfs.2011.10.012
[58] Hu MD, Guo GH . Advances in hepatic stellate cell-targeted treatment of hepatic fibrosis with bone marrow-derived mesenchymal stem cells[J]. Shi Jie Hua Ren Xiao Hua Za Zhi, 2010,18(24):2558-2562
[59] Rabani V, Shahsavani M, Gharavi M, Piryaei A, Azhdari Z, Baharvan H . Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression[J]. Cell Biol, 2010,34(6):601-605
[60] . Mesenchymal stem cells in the treatment of chronic liver disease — from experiment to clinical practice . Eksp Klin Gastroenterol. 2012; (6): 13-19. Russian with abstract in English.
[61] Abdel-Aziz MT, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Ahmed HH, Rashed LA, Sabry D, Hassouna AA, Hasan NM . Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis[J]. Clin Biochem, 2007,40(12):893-899
doi: 10.1016/j.clinbiochem.2007.04.017
[62] Dai LJ, Li HY, Guan LX, Ritchie G, Zhou JX . The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis[J]. Stem Cell Res, 2009,2(1):16-25
doi: 10.1016/j.scr.2008.07.005
[63] Deng X, Liang J, Liu ZW, Wu FS, Li X . Treatment of posthepatitic cirrhosis by Fuzheng Huayu Tablet for reinforcing qi and resolving stasis[J]. Chin J Integr Med, 2013,19(4):289-296
doi: 10.1007/s11655-013-1433-7
[64] Li X, Wang YL . Salvianolic acid B and tanshinone IIA induce bone marrow mesenchymal stem cells to differentiate into cardiomyocyte-like cells[J]. Zhongguo Zu Zhi Gong Cheng Yan Jiu, 2013,17(10):1849-1855
[65] Li SH, Guo PD, Wang WJ . Research progress of bone marrow mesenchymal stem cells differentiation into nerve-like cells induced by traditional Chinese medicine[J]. Zhongguo Gu Shang, 2010,23(3):233-235
[66] Zhong J, Cao H, Chen Z, Zhou F, Tan X . Wnt signaling pathways participate in Astragalus injection-induced differentiation of bone marrow mesenchymal stem cells[J]. Neurosci Lett, 2013,553:29-34
doi: 10.1016/j.neulet.2013.08.007
[67] Zheng H, Liu C, Ou Y, Zhang Y, Fu X . Total saponins of Panax notoginseng enhance VEGF and relative receptors signals and promote angiogenesis derived from rat bone marrow mesenchymal stem cells[J]. J Ethnopharmacol, 2013,147(3):595-602
doi: 10.1016/j.jep.2013.03.043
[68] Bian Q, Liu SF, Huang JH, Yang Z, Tang DZ, Zhou Q, Ning Y, Zhao YJ, Lu S, Shen ZY, Wang YJ . Oleanolic acid exerts an osteoprotective effect in ovariectomy-induced osteoporotic rats and stimulates the osteoblastic differentiation of bone mesenchymal stem cells in vitro[J]. Menopause, 2012,19(2):225-233
doi: 10.1097/gme.0b013e3182272ef1
[69] Zeng JC, Fan YG, Liu JR, Zeng YR, Yi CZ, Yan L . Experimental study of directional differentiation of bone mesenchymal stem cells(BMSCs) to osteoblasts guided by serum containing cistanche deserticola[J]. Zhongguo Gu Shang, 2010,23(8):606-608
[70] Yan BY, Dong FS, Wang J, Hao FL, Dong YY, Hu QH . Effects of traditional Chinese medicine on the differentiation of mesenchymal stem cells to osteoblasts[J]. Zhonghua Kou Qiang Yi Xue Za Zhi, 2010,45(1):31-35
[71] Zhang P, Dai KR, Yan SG, Yan WQ, Zhang C, Chen DQ, Xu B, Xu ZW . Effects of naringin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cell[J]. Eur J Pharmacol, 2009,607(1-3):1-5
doi: 10.1016/j.ejphar.2009.01.035
[72] Wei YJ, Tsai KS, Lin LC, Lee YT, Chi CW, Chang MC, Tsai TH, Hung SC . Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal stem cells[J]. Osteoporos Int, 2011,22(5):1469-1479
doi: 10.1007/s00198-010-1352-9
[73] Li G, Zhang XA, Zhang JF, Chan CY, Yew DT, He ML, Lin MC, Leung PC, Kung HF . Ethanol extract of Fructus Ligustri Lucidi promotes osteogenesis of mesenchymal stem cells[J]. Phytother Res, 2010,24(4):571-576
[74] Zhang JF, Li G, Chan CY, Meng CL, Lin MC, Chen YC, He ML, Leung PC, Kung HF . Flavonoids of Herba Epimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt/β-catenin signaling pathway[J]. Mol Cell Endocrinol, 2010,314(1):70-74
doi: 10.1016/j.mce.2009.08.012
[75] Zhang Y, Wang Y, Wang L, Zhang Y, Qin Y, Chen T, Han W, Chen G . Effects of Rehmannia glutinosa oligosaccharide on human adipose-derived mesenchymal stem cells in vitro[J]. Life Sci, 2012,91(25-26):1323-1327
doi: 10.1016/j.lfs.2012.10.015
[76] Wu G, Peng J, Wu M, Li Y, Huang Y, Lin R, Cai Q, Liu X . Experimental study of low-frequency electroacupuncture-induced differentiation of bone marrow mesenchymal stem cells into chondrocytes[J]. Int J Mol Med, 2011,27(1):79-86
[77] Xie J, Wang W, Si JW, Miao XY, Li JC, Wang YC, Wang ZR, Ma J, Zhao XC, Li Z, Yi H, Han H . Notch signaling regulates CXCR4 expression and the migration of mesenchymal stem cells[J]. Cell Immunol, 2013,281(1):68-75
doi: 10.1016/j.cellimm.2013.02.001
[78] Wang TT, Chen W, Zeng HP, Chen DF . Chemical components in extracts from Plastrum testudinis with proliferation-promoting effects on rat mesenchymal stem cells[J]. Chem Biol Drug Des, 2012,79(6):1049-1055
doi: 10.1111/jpp.2012.79.issue-6
[79] Chen DF, Zeng HP, Du SH, Li H, Zhou JH, Li YW, Wang TT, Hua ZC . Extracts from Plastrum testudinis promote proliferation of rat bone-marrow-derived mesenchymal stem cells[J]. Cell Prolif, 2007,40(2):196-212
doi: 10.1111/cpr.2007.40.issue-2
[80] Wei JA, Cheng ZA, Wen JX . Comparative study of enhancing effect on mRNA expression of hematopoietic growth factors in rat bone marrow mesenchymal stem cells by ginseng polysaccharide and ginsenoside[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2011,31(3):372-375
[81] Zeng HP, Wang TT, Chen W, Wang CY, Chen DF, Shen JG . Characterization of chemical components in extracts from Si-wu decoction with proliferation-promoting effects on rat mesenchymal stem cells[J]. Bioorg Med Chem, 2008,16(9):5109-5114
doi: 10.1016/j.bmc.2008.03.024
[82] Chen DF, Li X, Xu Z, Liu X, Du SH, Li H, Zhou JH, Zeng HP, Hua ZC . Hexadecanoic acid from Buzhong Yiqi Decoction induced proliferation of bone marrow mesenchymal stem cells[J]. J Med Food, 2010,13(4):967-975
doi: 10.1089/jmf.2009.1293
[83] Qiao H, Tong Y, Han H, Xu W, Ren Z, Ouyang J, Chen Y . A novel therapeutic regimen for hepatic fibrosis using the combination of mesenchymal stem cells and baicalin[J]. Pharmazie, 2011,66(1):37-43
[84] Ouyang J, Gao Z, Ren Z, Hong D, Qiao H, Chen Y . Synergistic effects of rMSCs and salidroside on the experimental hepatic fibrosis[J]. Pharmazie, 2010,65(8):607-613
[85] Zhang YK, Han XY, Che ZY . Effects of Buyang Huanwu Tang combined with bone marrow mesenchymal stem cell transplantation on the expression of VEGF and Ki-67 in the brain tissue of the cerebral ischemia-reperfusion model rat[J]. J Tradit Chin Med, 2010,30(4):278-282
doi: 10.1016/S0254-6272(10)60056-8
[86] Liu Z, Ding Y, Zeng YS . A new combined therapeutic strategy of governor vessel electro-acupuncture and adult stem cell transplantation promotes the recovery of injured spinal cord[J]. Curr Med Chem, 2011,18(33):5165-5171
doi: 10.2174/092986711797636144
[87] Sensebé L, Fleury-Cappellesso S . Biodistribution of mesenchymal stem/stromal cells in a preclinical setting[J]. Stem Cells Int, 2013,2013:678063
[88] Wang PP, Xie DY, Liang XJ, Peng L, Zhang GL, Ye YN, Xie C, Gao ZL . HGF and direct mesenchymal stem cells contact synergize to inhibit hepatic stellate cells activation through TLR4/NF-κB pathway[J]. PLoS One, 2012,7(8):e43408
doi: 10.1371/journal.pone.0043408
[1] Brody Slostad, Tejinder Khalsa, Kathleen Young, Hildalicia Guerra, Anjali Bhagra. A case-based approach to integrative medicine for cardiovascular disease prevention. Journal of Integrative Medicine, 2020, 18(2): 159-162.
[2] Ameena Yasmeen, Ghulamuddin Sofi, Kaleemullah Khan. Aamar-e-Advia (shelf-lives) of drugs in Unani system of medicine: A conceptual review. Journal of Integrative Medicine, 2020, 18(2): 114-124.
[3] Louisa Sylvia, Emerson West, Allyson M. Blackburn, Carina Gupta, Eric Bui, Tara Mahoney, Geraldine Duncan, Edward C. Wright, Simon Lejeune, Thomas J. Spencer. Acceptability of an adjunct equine-assisted activities and therapies program for veterans with posttraumatic stress disorder and/or traumatic brain injury. Journal of Integrative Medicine, 2020, 18(2): 169-173.
[4] Sherman Gu, Arthur Yin Fan. Controversial conclusions from two randomized controlled trials for acupuncture's effects on polycystic ovary syndrome or in vitro fertilization support. Journal of Integrative Medicine, 2020, 18(2): 89-91.
[5] Xue-qing Yu, Shu-guang Yang, Yang Xie, Jian-sheng Li. Traditional Chinese medicine in the treatment of idiopathic pulmonary fibrosis based on syndrome differentiation: Study protocol of exploratory trial. Journal of Integrative Medicine, 2020, 18(2): 163-168.
[6] Chang-quan Ling. Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2). Journal of Integrative Medicine, 2020, 18(2): 87-88.
[7] Sajjad Sadeghi, Farzaneh Ghaffari, Ghazaleh Heydarirad, Mehdi Alizadeh. Galen’s place in Avicenna’s The Canon of Medicine : Respect, confirmation and criticism. Journal of Integrative Medicine, 2020, 18(1): 21-25.
[8] Maryam Naeimia, Narjes Gorjib, Zahra Memarianib, Reihaneh Moeinib, Mohammad Kamalinejadc, Fatemeh Kolangid. Gastroprotective herbs for headache management in Persian medicine: A comprehensive review. Journal of Integrative Medicine, 2020, 18(1): 1-13.
[9] Mohadeseh Ostovar, Abolfazl Akbari, Mohammad Hossein Anbardar, Aida Iraji, Mohsen Salmanpour, Salar Hafez Ghoran, Mojtaba Heydari, Mesbah Shams. Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy. Journal of Integrative Medicine, 2020, 18(1): 59-67.
[10] Preecha Nootim, Nattiya Kapol, Waranee Bunchuailua, Panoopat Poompruek, Parankul Tungsukruthai . Current state of cancer patient care incorporating Thai traditional medicine in Thailand: A qualitative study. Journal of Integrative Medicine, 2020, 18(1): 41-45.
[11] Naghmeh Yazdi, Alireza Salehi, Mina Vojoud, Mohammad Hossein Sharifi, Ayda Hoseinkhani. Use of complementary and alternative medicine in pregnant women: a cross-sectional survey in the south of Iran. Journal of Integrative Medicine, 2019, 17(6): 392-395.
[12] Wen Qiang Lee, Jeremy Teoh, Pei Zheng Kenneth Lee, Zhi Xiong Gerard Low, Xueling Sim, Foong Fong Mary Chong, Norbert Ludwig Wagner. Factors influencing communication of traditional Chinese medicine use between patients and doctors: a multisite cross-sectional study. Journal of Integrative Medicine, 2019, 17(6): 396-403.
[13] Md. Anzar Alam, Mohd Aleemuddin Quamri, Ghulamuddin Sofi, Barkati Md.Tarique. Understanding hypothyroidism in Unani medicine. Journal of Integrative Medicine, 2019, 17(6): 387-391.
[14] Zienab Mahmoudpour, Javad Shokri, Mohammad Kamalinejad, Neda Meftah, Soraya Khafri, Seyyed Ali Mozaffarpur, Hoda Shirafkan. The efficacy of a Persian herbal formulation on functional bloating: A double-blind randomized controlled trial. Journal of Integrative Medicine, 2019, 17(5): 344-350.
[15] Rebecca Kulbida, Alexander Mathes, Johannes Loeser. Beneficial effects of hirudotherapy in a chronic case of complex regional pain syndrome. Journal of Integrative Medicine, 2019, 17(5): 383-386.
Full text



[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[3] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[4] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[5] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[6] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[7] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[8] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[9] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[10] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013