Abstract Liver injury has a high incidence in pet clinical cases, which can be caused by many factors. In recent years, with the development of cell therapy research, mesenchymal stem cell (MSCs) transplantation has gradually become a hot spot and main directions in the treatment of liver injury. At present, drug-induced animal models are the main research methods in the treatment of liver injury. It is very important to select a suitable and effective method to induce MSCs differentiate into hepatocytes. Some studies have shown that the treatment of MSCs with melatonin (Mel) can improve their viability in vitro and enhance the effect of transplantation therapy. It is also used in the treatment of diseases. In this review, adipose-derived mesenchymal stem cells (ADSCs) combined with melatonin transplantation for the treatment of liver injury are systematically described, which will provide a theoretical basis and guidance for further study.
YAN Yuan,LI Shu-Ying,MOU Yuan, et al. Progress of Adipose-derived Mesenchymal Stem Cells Combined with Melatonin in Treatment of Liver Injury[J]. 农业生物技术学报, 2019, 27(11): 2073-2082.
[1] 洪汝涛, 许建明, 沈继龙, 等. 2012. 褪黑素对大鼠肝纤维化的影响及部分机制研究[J]. 中国药理学通报, 28(8):1141-1145. (Hong R T, Xu J M, Shen J L, et al.2012. Effects of melatonin on hepatic fibrosis induced by carbon tetrachloride in rats and its mechanisms[J]. Chinese Pharmacological Bulletin, 28(8):1141-1145.) [2] 王于, 连帆, 谭国胜, 等. 2010. 同种异体脂肪干细胞门脉移植对大鼠纤维化肝脏的影响[J]. 中国病理生理杂志, 26(11): 2197-2201. (Wang Y, Lian F, Tan G S, et al.2010. Effect of portal vein transplantation with allogeneic adipose tissue-derived mesenchymal stem cells. Chinese Journal of Pathophysiology, 26(11): 2197-2201.) [3] Banas A, Teratani T Y, Tokuhara M, et al.2010. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure[J]. Journal of Gastroenterology, 24(1): 70-77. [4] Biburger M, Tiegs G.2005. α-galactosylceramide-induced liver injury in mice is mediated by TNF-α but independent of Kupffer cells[J]. The Journal of Immunology, 175(3):1540-1550. [5] Blaber S P, Webster R A, Hill C J, et al.2012. Analysis of in vitro secretion profiles from adipose-derived cell populations[J]. Journal of Translational Medicine, 10(1): 172. [6] Bochev I, Elmadjian G, Kyurkchiev D, et al.2013. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitro[J]. Cell Biology International, 32(4): 384-393. [7] Chang C, Sung P, Sun C, et al.2015. Protective effect of melatonin-supported adipose‐derived mesenchymal stem cells against small bowel ischemia‐reperfusion injury in rat[J]. Journal of Pineal Research, 59(2): 206-220. [8] Chen G, Jin Y, Shi X, et al.2015a. Adipose-derived stem cell-based treatment for acute liver failure[J]. Stem Cell Research & Therapy, 6(1): 40. [9] Chen J, Sun X, Xia T, et al.2018. Pretreatment with dihydroquercetin, a dietary flavonoid, protected against concanavalin A-induced immunological hepatic injury in mice and TNF-α/ActD-induced apoptosis in HepG2 Cells[J]. Food & Function, 9(4): 2341-2352. [10] Chen YT, Chiang HJ, Chen CH, et al.2015b. Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat[J]. Journal of Pineal Research, 57(3):248-261. [11] Choi H S, Kang J W, Lee S M.2015. Melatonin attenuates carbon tetrachloride-induced liver fibrosis via inhibition of necroptosis[J]. Translational Research, 166(3):292-303. [12] da Silva Meirelles L, Chagastelles P C, Nardi N B.2006. Mesenchymal stem cells reside in virtually all post-natal organs and tissues[J]. Journal of Cell Science, 119(11):2204-2213. [13] Freitas I, Bertone V, Guarnaschelli C, et al.2006. In situ demonstration of improvement of liver mitochondria function by melatonin after cold ischemia[J]. In Vivo, 20(2):229-237. [14] Ge Y, Zhang Q, Jiao Z, et al.2018a. Adipose-derived stem cells reduce liver oxidative stress and autophagy induced by ischemia-reperfusion and hepatectomy injury in swine[J]. Life Sciences, 214: 62-69. [15] Ge Y, Zhang Q, Li H, et al.2018b. Adipose-derived stem cells alleviate liver apoptosis induced by ischemia-reperfusion and laparoscopic hepatectomy in swine[J]. Scientific Reports, 8(1):16878. [16] Gong X, Yang Y, Huang L, et al.2017. Antioxidation, anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice[J]. International Immunopharmacology, 46: 124-132. [17] Guan X, Wang N, Cui F, et al.2016. Caveolin-1 is essential in the differentiation of human adipose-derived stem cells into hepatocyte-like cells via an MAPK pathway-dependent mechanism[J]. Molecular Medicine Reports, 13(2): 1487-1494. [18] Guo D L, Wang Z G, Xiong L K, et al.2016. Hepatogenic differentiation from human adipose-derived stem cells and application for mouse acute liver injury[J]. Artificial Cells, Nanomedicine, and Biotechnology, 45(2):224-232. [19] Hajinejad M, Pasbakhsh P, Omidi A, et al.2018. Resveratrol pretreatment enhanced homing of SDF-1α-preconditioned bone marrow-derived mesenchymal stem cells in a rat model of liver cirrhosis[J]. Journal of Cellular Biochemistry, 119(3): 2939-2950. [20] He Z, Hua J, Qian D, et al.2016. Intravenous hMSCs Ameliorate acute pancreatitis in mice via secretion of tumor necrosis factor-α stimulated gene/protein 6[J]. Scientific Reports, 6: 38438. [21] Heike B, Klaus S O.2012. Mechanisms of cell death in acute liver failure[J]. Frontiers in Physiology, 3: 79. [22] Higashimoto M, Sakai Y, Takamura M, et al.2013. Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4 + T-cell suppression[J]. European Journal of Immunology, 43(11): 2956-2968. [23] Hou Y, Liu L, Chai J, et al.2015. Lipopolysaccharide pretreatment inhibits LPS-induced human umbilical cord mesenchymal stem cell apoptosis via upregulating the expression of cellular FLICE-inhibitory protein[J]. Molecular Medicine Reports, 12(2): 2521-2528. [24] Huang B, Cheng X, Wang H, et al.2016. Mesenchymal stem cells and their secreted molecules predominantly ameliorate fulminant hepatic failure and chronic liver fibrosis in mice respectively[J]. Journal of Translational Medicine, 14: 45. [25] Imaeda A B, Watanabe A, Sohail M A, et al.2009. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome[J]. Journal of Clinical Investigation, 119(2): 305-314. [26] Jang Y O, Kim S H, Cho M Y, et al.2018. Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis[J]. Biochemical and Biophysical Research Communications, 497(1): 264-271. [27] Jiang W, Sun R, Wei H, et al.2005. Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll-like receptor 4 expression on macrophages[J]. Proceedings of the National Academy of Sciences of the USA, 102(47): 17077-17082. [28] Kang J W, Hong J M, Lee S M.2016. Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis[J]. Journal of Pineal Research, 60(4): 383-393. [29] Kaundal U, Bagai U, Rakha A.2018. Immunomodulatory plasticity of mesenchymal stem cells: A potential key to successful solid organ transplantation[J]. Journal of Translational Medicine, 16(1): 31. [30] Kus I, Ogeturk M, Oner H, et al.2005. Protective effects of melatonin against carbon tetrachloride-induced hepatotoxicity in rats: A light microscopic and biochemical study[J]. Cell Biochemistry & Function, 23(3): 169-174. [31] Lee J H, Lee K H, Kim M H, et al.2012. Possibility of undifferentiated human thigh adipose stem cells differentiating into functional hepatocytes[J]. Archives of Facial Plastic Surgery, 39(6): 593-599. [32] Lee M S, Yin T C, Sung P H, et al.2016. Melatonin enhances survival and preserves functional integrity of stem cells: A review[J]. Journal of Pineal Research, 62(2): :e12372. [33] Li Q, Qi L J, Guo Z K, et al.2013. CD73 adipose-derived mesenchymal stem cells possess higher potential to differentiate into cardiomyocytes in vitro[J]. Journal of Molecular Histology, 44(4): 411-422. [34] Liu X, Gong Y, Xiong K, et al.2013. Melatonin mediates protective effects on inflammatory response induced by interleukin-1 beta in human mesenchymal stem cells[J]. Journal of Pineal Research, 55(1): 14-25. [35] Lu Y, Tian C, Gao C, et al.2018. Nutritional profiles, phenolics, and DNA damage protective effect of Lycopus lucidus Turcz. root at different harvest times[J]. International Journal of Food Properties, 20(3):3 062-3077. [36] Man K, Shih KC, Ng KT, et al.2010. Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts[J]. Annals of Surgery, 251(6):1154-1161. [37] Mias C, Trouche E, Seguelas MH, et al.2008. Ex Vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney[J]. Stem Cells, 26(7): 1749-1757. [38] Mortezaee K, Sabbaghziarani F, Omidi A, et al.2015. Therapeutic value of melatonin post-treatment on CCl4-induced fibrotic rat liver[J]. Canadian Journal of Physiology & Pharmacology, 94(2): 119-130. [39] Nascimento M, Piran R, da Costa R M, et al.2018. Hepatic injury induced by thioacetamide causes aortic endothelial dysfunction by a cyclooxygenase-dependent mechanism[J]. Life Sciences, 212: 168-175. [40] Nasir G A, Mohsin S, Khan M, et al.2013. Mesenchymal stem cells and Interleukin-6 attenuate liver fibrosis in mice[J]. Journal of Translational Medicine, 11(1): 78. [41] Ničković V P, Novaković T, Lazarević S,et al.2018. Pre- vs. post-treatment with melatonin in CCl4-induced liver damage: Oxidative stress inferred from biochemical and pathohistological studies[J]. Life Sciences, 202: 28-34. [42] Ning J W, Zhang Y, Yu M S, et al.2017. Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition[J]. Hepatobiliary & Pancreatic Diseases International, 16(4): 431-436. [43] Nishino M, Iimuro Y, Ueki T, et al.2008. Hepatocyte growth factor improves survival after partial hepatectomy in cirrhotic rats suppressing apoptosis of hepatocytes[J]. Surgery, 144(3): 374-384 [44] Noyan T, Komuroglu U, Bayram I, et al.2006. Comparison of the effects of melatonin and pentoxifylline on carbon tetrachloride-induced liver toxicity in mice[J]. Cell Biology and Toxicology, 22(6): 381-391. [45] Ohta Y, Kongo M, Sasaki E, et al.2000. Therapeutic effect of melatonin on carbon tetrachloride-induced acute liver injury in rats[J]. Journal of Pineal Research, 28(2): 119-126. [46] Okatani Y, Wakatsuki A, Reiter R J, et al.2003. Protective effect of melatonin against mitochondrial injury induced by ischemia and reperfusion of rat liver[J]. European Journal of Pharmacology, 469(1-3): 145-152. [47] Parekkadan B, Milwid JM.2010. Mesenchymal stem cells as therapeutics[J]. Annual review of biomedical engineering, 12(1): 87-117. [48] Patsenker E, Chicca A, Petrucci V, et al.2017. 4-O′-methylhonokiol protects from alcohol/carbon tetrachloride-induced liver injury in mice[J]. Journal of molecular medicine (Berlin, Germany), 95(10): 1-13. [49] Qiao H, Tong Y, Han H,et al.2011. A novel therapeutic regimen for hepatic fibrosis using the combination of mesenchymal stem cells and baicalin[J]. Pharmazie, 66(1): 37-43. [50] Ribeiro A, Laranjeira P, Mendes S, et al.2013. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells[J]. Stem Cell Research & Therapy, 4(5): 125-125. [51] Rodniem S, Tiyao V, Nilbu-Nga C, et al.2018. Protective effect of alpha-mangostin on thioacetamide-induced liver fibrosis in rats as revealed by morpho-functional analysis.[J]. Histology and Histopathology, 34(4): 419-430. [52] Rodriguez-Reynoso S, Leal C, Portilla E, et al.2001. Effect of exogenous melatonin on hepatic energetic status during ischemia/reperfusion: possible role of tumor necrosis factor-alpha and nitric oxide[J]. Journal of Surgical Research, 100(2): 141-149. [53] Ryu K H, Kim S Y, Kim Y R, et al.2014. Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury.[J]. Experimental Cell Research, 326(1): 143-154. [54] Seki A, Sakai Y, Komura T, et al.2013. Adipose tissue-derived stem cells as a regenerative therapy for a murine steatohepatitis-induced cirrhosis model[J]. Hepatology, 58(3): 1133-1142. [55] Seki T, Yokoyama Y, Nagasaki H, et al.2012. Adipose tissue-derived mesenchymal stem cell transplantation promotes hepatic regeneration after hepatic ischemia-reperfusion and subsequent hepatectomy in rats[J]. The Journal of surgical research, 178(1): 63-70. [56] Shen H, Kormpakis I, Havlioglu N, et al.2016. The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing[J]. Stem Cell Research & Therapy, 7(1): 144. [57] Shiga A, Kakamu S, Sugiyama Y, et al.2006. Acute toxicity of pierisin-1, a cytotoxic protein from Pieris rapae, in mouse and rat[J]. The Journal of Toxicological Sciences, 31(2): 123-137. [58] Shiota G, Itaba N.2017. Progress in stem cell‐based therapy for liver disease[J]. Hepatology Research, 47(2): 127-141. [59] Tang W P, Akahoshi T, Piao J S, et al.2015. Basic fibroblast growth factor-treated adipose tissue-derived mesenchymal stem cell infusion to ameliorate liver cirrhosis via paracrine hepatocyte growth factor[J]. Journal of Gastroenterology and Hepatology, 30(6): 1065-1074. [60] Teshima T, Matsumoto H, Michishita M, et al.2017. Allogenic adipose tissue-derived mesenchymal stem cells ameliorate acute hepatic injury in dogs[J]. Stem Cells International, 2017: 1-12. [61] Tian Y, Wang J, Wang W, et al.2016. Mesenchymal stem cells improve mouse non-heart-beating liver graft survival by inhibiting Kupffer cell apoptosis via TLR4-ERK1/2-Fas/FasL-caspase3 pathway regulation[J]. Stem Cell Research & Therapy, 7(1): 157. [62] Vanikar A V, Trivedi H L, Feroze A, et al.2011. Effect of co-transplantation of mesenchymal stem cells and hematopoietic stem cells as compared to hematopoietic stem cell transplantation alone in renal transplantation to achieve donor hypo-responsiveness[J]. International Urology and Nephrology, 43(1): 225-232. [63] Wang H, Wei W, Wang N P, et al.2005. Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress[J]. Life Sciences, 77(15):1902-1915. [64] Wang L, Tu L, Zhang J, et al.2017. Stellate cell activation and imbalanced expression of TGF-β1/TGF-β3 in acute autoimmune liver lesions induced by ConA in mice[J]. BioMed Research International, 2017(3): 2540540. [65] Wang Y, Wang F, Zhao H, et al.2014. Human adipose-derived mesenchymal stem cells are resistant to HBV infection during differentiation into hepatocytes in vitro[J]. International Journal of Molecular Sciences, 15(4):6096-6110. [66] Wang Y, Zhang Z, Chi Y, et al.2013. Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation[J]. Cell Death & Disease, 4(12): e950. [67] Xiong X, Ren Y, Cui Y, et al.2017. Obeticholic acid protects mice against lipopolysaccharide -induced liver injury and inflammation[J]. Biomedicine & Pharmacotherapy, 96: 1292-1298. [68] Yan Y, Fang J, Wen X, et al.2019. Therapeutic applications of adipose-derived mesenchymal stem cells on acute liver injury in canines[J]. Research in Veterinary Science (In press), DOI:10.1016/j.rvsc.2019.09.004. [69] Yin L, Zhu Y, Yang J, et al.2015. Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro[J]. Molecular Medicine Reports, 11(3): 1722-1732. [70] Zhang S, Zhu Z, Wang Y, et al.2018. Therapeutic potential of Bama miniature pig adipose stem cells induced hepatocytes in a mouse model with acute liver failure[J]. Cytotechnology, 70(4): 1131-1141. [71] Zheng X Y, Zhao X, Yang Y F, et al.2017. Antioxidant, antiapoptotic and amino acid balance regulating activities of 1,7-dihydroxy-3,4,8-trimethoxyxanthone against dimethylnitrosamine -induced liver fibrosis.[J]. PLOS ONE, 12(12): e0189344. [72] Zhou L, Chen X, Liu T, et al.2015. Melatonin reverses H2O2-induced premature senescence in mesenchymal stem cells via the SIRT1-dependent pathway[J]. Journal of Pineal Research, 59(2): 190-205. [73] Zhu X, Zhang B, Zhao H, et al.2015. Jagged-2 enhances immunomodulatory activity in adipose derived mesenchymal stem cells[J]. Scientific Reports, 5: 14284.
