Human adipose-derived mesenchymal stem cells promote liver cell regeneration by up-regulating the expression of proliferating cell nuclear antigen

doi:10.3969/j.issn.2095-4344.2017.17.011

Abstract

Abstract:

BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) can improve the liver function of rats with liver failure, which illustrates the important research value in the field of tissue engineering and cell transplantation.
OBJECTIVE: To evaluate the therapeutic potential of human ADMSCs in heart failure rats and to discuss the possible biological mechanisms involved.
METHODS: Heart failure rats were randomized into model and ADMSCs groups, which were given normal saline or DAPI-labeled human ADMSCs (3.0×10⁶) via the tail vein. At 1, 3, 7 days after transplantation, we detected the biochemical indexes for liver function in rats. At 3 days after transplantation, the serum levels of cytokines, such as tumor necrosis factor α and interleukin-10, were detected, the histomorphological changes in the liver were observed by hematoxylin-eosin staining, and the protein expression of proliferating cell nuclear antigen was detected by western blot.
RESULTS AND CONCLUSION: We found that human ADMSCs could migrate to the liver and lung tissues in rats after the transplantation via the tail vein. At 1 and 3 days after transplantation, the levels of serum alanine aminotransferase and aspartate aminotransferase were significantly reduced in the ADMSCs group as compared with the model group (P < 0.05); furthermore, the secretion of tumor necrosis factor α and interleukin-10 was significantly suppressed at 3 days after cell transplantation (P < 0.05). The results of hematoxylin-eosin staining indicated a significant improvement in liver degeneration and necrosis. The expression of proliferating cell nuclear antigen protein in the ADMSCs group was significantly up-regulated compared with the model group. To conclude, human ADMSCs can inhibit the inflammatory reaction and up-regulate the expression of proliferating cell nuclear antigen, to promote the regeneration of liver cells and the recovery of liver function.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Adipose Tissue, Mesenchymal Stem Cell Transplantation, Liver Failure, Acute, Proliferating Cell Nuclear Antigen, Tissue Engineering

CLC Number:

R394.2

Shi Guang-jun, Zhang Ya-dong, Hu Yin-yin, Tan Xue-ying. Human adipose-derived mesenchymal stem cells promote liver cell regeneration by up-regulating the expression of proliferating cell nuclear antigen[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(17): 2690-2695.

Figures/Tables 3

References

[1] Dhawan A, Puppi J, Hughes RD, et al. Human hepatocyte transplantation: current experience and future challenges. Nat Rev Gastroenterol Hepatol. 2010;7(5):288-298.

[2] Tralhão JG, Abrantes AM, Hoti E, et al. Hepatectomy and liver regeneration: from experimental research to clinical application. ANZ J Surg. 2014;84(9):665-671.

[3] Pham PV. Adipose stem cells in the clinic. Biomedical Research Therapy. 2014;1(2):57-70.

[4] Kubo N, Narumi S, Kijima H, et al. Efficacy of adipose tissue-derived mesenchymal stem cells for fulminant hepatitis in mice induced by concanavalin A. J Gastroenterol Hepatol. 2012;27(1):165-172.

[5] Harn HJ, Lin SZ, Hung SH, et al. Adipose-derived stem cells can abrogate chemical-induced liver fibrosis and facilitate recovery of liver function. Cell Transplant. 2012;21(12): 2753-2764.

[6] Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-228.

[7] Banas A, Teratani T, Yamamoto Y, et al. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J Gastroenterol Hepatol. 2009;24(1):70-77.

[8] Yukawa H, Noguchi H, Oishi K, et al. Cell transplantation of adipose tissue-derived stem cells in combination with heparin attenuated acute liver failure in mice. Cell Transplant. 2009; 18(5):611-618.

[9] Ranganath SH, Levy O, Inamdar MS, et al. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell. 2012;10(3):244-258.

[10] Chung H, Hong DP, Jung JY, et al. Comprehensive analysis of differential gene expression profiles on carbon tetrachloride-induced rat liver injury and regeneration. Toxicol Appl Pharmacol. 2005;206(1):27-42.

[11] 杨志峰,杨清玲, 陈昌杰. 趋化因子SDF-1与受体CXCR4的研究进展[J]. 分子诊断与治疗杂志, 2011, 3(1):58-61.

[12] Ezzat T, Dhar DK, Malago M, et al. Dynamic tracking of stem cells in an acute liver failure model. World J Gastroenterol. 2012;18(6):507-516.

[13] Berry PA, Antoniades CG, Hussain MJ, et al. Admission levels and early changes in serum interleukin-10 are predictive of poor outcome in acute liver failure and decompensated cirrhosis. Liver Int. 2010;30(5):733-740.

[14] Tögel F, Hu Z, Weiss K, et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 2005;289(1):F31-42.

[15] Parekkadan B, van Poll D, Suganuma K, et al. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One. 2007;2(9):e941.

[16] Higashimoto M, Sakai Y, Takamura M, et al. Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4+ T-cell suppression. Eur J Immunol. 2013;43(11):2956-2968.

[17] Du Z, Wei C, Cheng K, et al. Mesenchymal stem cell-conditioned medium reduces liver injury and enhances regeneration in reduced-size rat liver transplantation. J Surg Res. 2013;183(2):907-915.

[18] Salomone F, Barbagallo I, Puzzo L, et al. Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury. Stem Cell Res. 2013;11(3): 1037-1044.

[19] Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(2):105-136.

[20] O'Garra A, Barrat FJ, Castro AG, et al. Strategies for use of IL-10 or its antagonists in human disease. Immunol Rev. 2008;223:114-131.

[21] Serra MP, Marongiu F, Sini M, et al. Hepatocyte senescence in vivo following preconditioning for liver repopulation. Hepatology. 2012;56(2):760-768.

[22] Serra MP, Marongiu F, Sini M, et al. Hepatocyte senescence induced by radiation and partial hepatectomy in rat liver. Int J Radiat Biol. 2014;90(10):876-883.

[23] 马珊珊,刘静,姚宁,等. p16基因高表达对293细胞衰老的影响[J].郑州大学学报:医学版, 2014,49(5):622-625.

[24] Yu SL, Kang MS, Kim HY, et al. The PCNA binding domain of Rad2p plays a role in mutagenesis by modulating the cell cycle in response to DNA damage. DNA Repair (Amst). 2014;16:1-10.

[25] Seki A, Sakai Y, Komura T, et al. Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis- induced cirrhosis model. Hepatology. 2013;58(3):1133-1142.

[26] Seki T, Yokoyama Y, Nagasaki H, et al. Adipose tissue-derived mesenchymal stem cell transplantation promotes hepatic regeneration after hepatic ischemia-reperfusion and subsequent hepatectomy in rats. J Surg Res. 2012;178(1):63-70.

[27] Koellensperger E, Niesen W, Kolbenschlag J, et al. Human adipose tissue derived stem cells promote liver regeneration in a rat model of toxic injury. Stem Cells Int. 2013;2013: 534263.

[28] Liu T, Mu H, Shen Z, et al. Autologous adipose tissue?derived mesenchymal stem cells are involved in rat liver regeneration following repeat partial hepatectomy. Mol Med Rep. 2016; 13(3):2053-2059.