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, 易軍, 陳江, 等. 脂肪來源的間充質干細胞對大鼠心肌梗死后心功能的保護作用. 中國體外循環雜志, 2014, 12(1): 54-57.
4.	郭婷婷, 黎麗茜, 田虹. 脂肪干細胞修復泌尿系統損傷: 應用現狀及問題. 中國組織工程研究, 2014, 18(2): 283-288.
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6.	張善強, 李永濤, 孫石柱, 等. 神經營養因子-3 通過 Wnt 通路促進人骨髓間充質干細胞生長和成骨分化的研究. 中國現代醫學雜志, 2016, 26(15): 6-10.
7.	張守華, 楊慎華, 楊文萍, 等. c-Kit⁺Lin^-細胞移植改善急性肝損傷的實驗研究. 分子診斷與治療雜志, 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.	瞿海龍, 邊劍飛, 張冰, 等. 間充質干細胞臨床應用的前景與困惑. 醫學研究與教育, 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, 顧昕, 張娜, 等. 干擾素 $ \gamma $ 增強脂肪間充質干細胞對淋巴細胞的免疫調節作用. 天津醫藥, 2016, 44(6): 683-686.
16.	李文媛, 王瑩, 李智剛, 等. KLF7 聯合脂肪源性干細胞對小鼠坐骨神經缺損后軸突再生的影響. 中風與神經疾病雜志, 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.	崔剛, 姜浩, 金星林. Ki-67, VEGF, CyclinD1 的表達與肝細胞癌生物學行為的關系. 世界華人消化雜志, 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. ?房艷, 李德華, 倪偉民, 等. 人脂肪源性干細胞多潛能分化特性. 解剖科學進展, 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, 易軍, 陳江, 等. 脂肪來源的間充質干細胞對大鼠心肌梗死后心功能的保護作用. 中國體外循環雜志, 2014, 12(1): 54-57.
4. 郭婷婷, 黎麗茜, 田虹. 脂肪干細胞修復泌尿系統損傷: 應用現狀及問題. 中國組織工程研究, 2014, 18(2): 283-288.
5. Harasymiak-Krzy?anowska I, Niedojad?o 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. 張善強, 李永濤, 孫石柱, 等. 神經營養因子-3 通過 Wnt 通路促進人骨髓間充質干細胞生長和成骨分化的研究. 中國現代醫學雜志, 2016, 26(15): 6-10.
7. 張守華, 楊慎華, 楊文萍, 等. c-Kit⁺Lin^-細胞移植改善急性肝損傷的實驗研究. 分子診斷與治療雜志, 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. 瞿海龍, 邊劍飛, 張冰, 等. 間充質干細胞臨床應用的前景與困惑. 醫學研究與教育, 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, 顧昕, 張娜, 等. 干擾素 $ \gamma $ 增強脂肪間充質干細胞對淋巴細胞的免疫調節作用. 天津醫藥, 2016, 44(6): 683-686.
16. 李文媛, 王瑩, 李智剛, 等. KLF7 聯合脂肪源性干細胞對小鼠坐骨神經缺損后軸突再生的影響. 中風與神經疾病雜志, 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. 崔剛, 姜浩, 金星林. Ki-67, VEGF, CyclinD1 的表達與肝細胞癌生物學行為的關系. 世界華人消化雜志, 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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