Effect of pregnant rat adipose-derived stem cells on repair of acute liver injury_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Junnan ¹ ,  CHEN Jiayong ² , CHEN Zhong ¹ , YANG Hongchang ¹ , HOU Kaiyu ¹

1. Department of Bone and Trauma Surgery, the Fourth Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650000, P.R.China;
2. Department of Emergency Medicine, the Second Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650000, P.R.China;

Corresponding author：

CHEN Jiayong, Email: 315808424@qq.com

Keywords：

Acute liver injury; adipose-derived stem cells; pregnancy; rat

DOI：

10.7507/1002-1892.201610076

Video：

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Objective To assess the effect of pregnant rat adipose-derived stem cells (ADSCs) on repair of acute liver injury. Methods ADSCs were isolated from 18-week pregnant Sprague Dawley rats and were identified by flow cytometry. Twenty Sprague Dawley rats were randomly divided into groups A, B, C, and D (n=5); rats in group A were not treated as normal controls; rats in groups B, C, and D were injected intraperitoneally with CCl₄ to establish the acute liver injury model. At 2 hours after modeling, DPBS, 0.1 mL normal rat ADSCs (2×10⁶cells/mL), and pregnant rat ADSCs (2×10⁶cells/mL) were injected into the spleen in groups A, C, and D respectively; rats in group B was not treated. After 7 days, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartic acid transaminase (AST), albumin (ALB), and total protein (TP) in serum were measured. The liver tissue sections were stained with HE. The expressions of Ki67, alpha-fetoprotein (AFP), and ALB were measured by immunohistochemistry. Results The serum levels of TBIL, ALT, and AST in group B were significantly higher than those in groups A, C, and D (P<0.05), but ALB and TP were significantly lower than those in groups A, C, and D (P<0.05). The levels of TBIL, ALT, and AST were significantly higher in groups C and D than group A, and in group C than group D (P<0.05). There was no significant difference in serum levels of ALB among groups A, C, and D (P>0.05). The serum level of TP in groups C and D was significantly lower than that in group A (P<0.05), but no significant difference was found between group C and group D (P>0.05). HE staining showed that the liver tissue of group A had clear structure; the cells arranged neatly with uniform size. The hepatocytes in group B showed obvious edema, disorderly arrangement, dot necrosis in liver lobules, and diffuse infiltration of inflammatory cells. In groups C and D, the inflammation and hepatocellular necrosis were obviously reduced when compared with group B, and the number of vacuoles caused by dilation of mitochondria and rough endoplasmic reticulum was decreased; especially in group D, improvement of liver injury was more effective. The Ki67 positive cell rate was significantly higher in groups C and D than groups A and B (P<0.05), in group B than group A (P<0.05), and in group D than group C (P<0.05). There was no expression of AFP in groups A and B, but positive expression was observed in groups C and D, and AFP positive cell rate of group D was significantly higher than that of group C (t=3.006,P=0.017). ALB expression was significantly higher in groups C and D than groups A and B (P<0.05), and in group D than group C (P<0.05). Conclusion Pregnant rat ADSCs could promote repair of liver injury induced by CCl₄.

Citation： LI Junnan, CHEN Jiayong, CHEN Zhong, YANG Hongchang, HOU Kaiyu. Effect of pregnant rat adipose-derived stem cells on repair of acute liver injury. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(3): 357-362. doi: 10.7507/1002-1892.201610076 Copy

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2.	Sohrabi M, Hassani A, Karimi A, et al. Efficacy of adipose-derived stem cells for regeneration of localized mandibular bone defects. Journal of Craniomaxillofacial Research, 2015, 2(1): 151-156.
3.	李佳丹, 易军, 陈江, 等. 脂肪来源的间充质干细胞对大鼠心肌梗死后心功能的保护作用. 中国体外循环杂志, 2014, 12(1): 54-57.
4.	郭婷婷, 黎丽茜, 田虹. 脂肪干细胞修复泌尿系统损伤: 应用现状及问题. 中国组织工程研究, 2014, 18(2): 283-288.
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6.	张善强, 李永涛, 孙石柱, 等. 神经营养因子-3 通过 Wnt 通路促进人骨髓间充质干细胞生长和成骨分化的研究. 中国现代医学杂志, 2016, 26(15): 6-10.
7.	张守华, 杨慎华, 杨文萍, 等. c-Kit⁺Lin^-细胞移植改善急性肝损伤的实验研究. 分子诊断与治疗杂志, 2015, 7(6): 387-391.
8.	Gnecchi M, Danieli P, Malpasso G, et al. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair. Mesenchymal Stem Cells, 2016, 416: 123-146.
9.	Valle-Prieto A, Conget PA. Human mesenchymal stem cells efficiently manage oxidative stress. Stem Cells Dev, 2010, 19(12): 1885-1893.
10.	Wang Y, Yao HL, Cui CB, et al. Paracrine signals from mesenchymal cell populations govern the expansion and differentiation of human hepatic stem cells to adult liver fates. Hepatology, 2010, 52(4): 1443-1454.
11.	Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 2005, 105(4): 1815-1822.
12.	Aziz Mt Abdel, Atta Hm, Mahfouz S, et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin Biochem, 2007, 40(12): 893-899.
13.	瞿海龙, 边剑飞, 张冰, 等. 间充质干细胞临床应用的前景与困惑. 医学研究与教育, 2011, 28(5): 72-75.
14.	Razavi S, Razavi MR, Ahmadi N, et al. Estrogen treatment enhances neurogenic differentiation of human adipose derived stem cellsin vitro. Iran J Basic Med Sci, 2015, 18(8): 799-804.
15.	王平, 顾昕, 张娜, 等. 干扰素 $ \gamma $ 增强脂肪间充质干细胞对淋巴细胞的免疫调节作用. 天津医药, 2016, 44(6): 683-686.
16.	李文媛, 王莹, 李智刚, 等. KLF7 联合脂肪源性干细胞对小鼠坐骨神经缺损后轴突再生的影响. 中风与神经疾病杂志, 2016, 33(7): 580-583.
17.	Ng LW, Yip SK, Wong HK, et al. Adipose-derived stem cells from pregnant women show higher proliferation rate unrelated to estrogen. Hum Reprod, 2009, 24(5): 1164-1170.
18.	Li LT, Jiang G, Chen Q, et al. Ki67 is a promising molecular target in the diagnosis of cancer (Review). Mol Med Rep, 2015, 11(3): 1566-1572.
19.	崔刚, 姜浩, 金星林. Ki-67, VEGF, CyclinD1 的表达与肝细胞癌生物学行为的关系. 世界华人消化杂志, 2012, 20(27): 2622-2627.
20.	von Montfort C, Beier JI, Kaiser JP, et al. PAI-1 plays a protective role in CCl₄-induced hepatic fibrosis in mice: role of hepatocyte division. Am J Physiol Gastrointest Liver Physiol, 2010, 298(5): G657-666.
21.	Jung J, Moon JW, Choi JH, et al. Epigenetic alterations of IL-6/STAT3 signaling by placental stem cells promote hepatic regeneration in a rat model with CCl₄-induced liver injury. Int J Stem Cells, 2015, 8(1): 79-89.

1. 房艳, 李德华, 倪伟民, 等. 人脂肪源性干细胞多潜能分化特性. 解剖科学进展, 2013, 19(3): 213-217.
2. Sohrabi M, Hassani A, Karimi A, et al. Efficacy of adipose-derived stem cells for regeneration of localized mandibular bone defects. Journal of Craniomaxillofacial Research, 2015, 2(1): 151-156.
3. 李佳丹, 易军, 陈江, 等. 脂肪来源的间充质干细胞对大鼠心肌梗死后心功能的保护作用. 中国体外循环杂志, 2014, 12(1): 54-57.
4. 郭婷婷, 黎丽茜, 田虹. 脂肪干细胞修复泌尿系统损伤: 应用现状及问题. 中国组织工程研究, 2014, 18(2): 283-288.
5. Harasymiak-Krzyżanowska I, Niedojadło A, Karwat J, et al. Adipose tissue-derived stem cells show considerable promise for regenerative medicine applications. Cell Mol Biol Lett, 2013, 18(4): 479-493.
6. 张善强, 李永涛, 孙石柱, 等. 神经营养因子-3 通过 Wnt 通路促进人骨髓间充质干细胞生长和成骨分化的研究. 中国现代医学杂志, 2016, 26(15): 6-10.
7. 张守华, 杨慎华, 杨文萍, 等. c-Kit⁺Lin^-细胞移植改善急性肝损伤的实验研究. 分子诊断与治疗杂志, 2015, 7(6): 387-391.
8. Gnecchi M, Danieli P, Malpasso G, et al. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair. Mesenchymal Stem Cells, 2016, 416: 123-146.
9. Valle-Prieto A, Conget PA. Human mesenchymal stem cells efficiently manage oxidative stress. Stem Cells Dev, 2010, 19(12): 1885-1893.
10. Wang Y, Yao HL, Cui CB, et al. Paracrine signals from mesenchymal cell populations govern the expansion and differentiation of human hepatic stem cells to adult liver fates. Hepatology, 2010, 52(4): 1443-1454.
11. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 2005, 105(4): 1815-1822.
12. Aziz Mt Abdel, Atta Hm, Mahfouz S, et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin Biochem, 2007, 40(12): 893-899.
13. 瞿海龙, 边剑飞, 张冰, 等. 间充质干细胞临床应用的前景与困惑. 医学研究与教育, 2011, 28(5): 72-75.
14. Razavi S, Razavi MR, Ahmadi N, et al. Estrogen treatment enhances neurogenic differentiation of human adipose derived stem cellsin vitro. Iran J Basic Med Sci, 2015, 18(8): 799-804.
15. 王平, 顾昕, 张娜, 等. 干扰素 $ \gamma $ 增强脂肪间充质干细胞对淋巴细胞的免疫调节作用. 天津医药, 2016, 44(6): 683-686.
16. 李文媛, 王莹, 李智刚, 等. KLF7 联合脂肪源性干细胞对小鼠坐骨神经缺损后轴突再生的影响. 中风与神经疾病杂志, 2016, 33(7): 580-583.
17. Ng LW, Yip SK, Wong HK, et al. Adipose-derived stem cells from pregnant women show higher proliferation rate unrelated to estrogen. Hum Reprod, 2009, 24(5): 1164-1170.
18. Li LT, Jiang G, Chen Q, et al. Ki67 is a promising molecular target in the diagnosis of cancer (Review). Mol Med Rep, 2015, 11(3): 1566-1572.
19. 崔刚, 姜浩, 金星林. Ki-67, VEGF, CyclinD1 的表达与肝细胞癌生物学行为的关系. 世界华人消化杂志, 2012, 20(27): 2622-2627.
20. von Montfort C, Beier JI, Kaiser JP, et al. PAI-1 plays a protective role in CCl₄-induced hepatic fibrosis in mice: role of hepatocyte division. Am J Physiol Gastrointest Liver Physiol, 2010, 298(5): G657-666.
21. Jung J, Moon JW, Choi JH, et al. Epigenetic alterations of IL-6/STAT3 signaling by placental stem cells promote hepatic regeneration in a rat model with CCl₄-induced liver injury. Int J Stem Cells, 2015, 8(1): 79-89.

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