Effects of adipose-derived stem cells cultured with astragaloside on cisplatin-induced apoptosis of renal tubular epithelial cells

doi:10.3969/j.issn.2095-4344.2014.28.012

Abstract

Abstract:

BACKGROUND: The validity of stem cell transplantation for acute kidney injury has been verified by many studies. However, the mechanism of repair of tubular epithelial cell injury remains unclear.
OBJECTIVE: To investigate protective effects and mechanisms of adipose-derived stem cells cultured with astragaloside on the apoptosis of renal tubular epithelial cells induced by cisplatin.
METHODS: There were four groups. Renal tubular epithelial cells were induced by 2.5 μmol/L cisplatin for 24 hours. Models of renal tubular cell injury were established in the cisplatin group. Adipose-derived stem cells were cocultured with renal tubular epithelial cells of injured kidney in the adipose-derived stem cells + renal tubular epithelial cells group. Using Transwell chamber, adipose-derived stem cells were incubated with 20 mg/L astragaloside for 48 hours, and then cocultured with renal tubular epithelial cells in the astragaloside-incubated adipose-derived stem cells + renal tubular epithelial cells group. Normal renal tubular epithelial cells served as controls (normal control group).
RESULTS AND CONCLUSION: Compared with renal tubular epithelial cell injury group, AV/PI and TUNEL results demonstrated that the apoptotic rate and number of renal tubular epithelial cells were apparently reduced in the adipose-derived stem cells + renal tubular epithelial cells group and 20 mg/L astragaloside-incubated adipose-derived stem cells + renal tubular epithelial cells group. ELISA results displayed that insulin-like growth factor-1 levels were significantly elevated in the 20 mg/L astragaloside-incubated adipose-derived stem cells + renal tubular epithelial cells group (P < 0.05). Western blot assay results exhibited that caspase-3 protein levels were noticeably diminished, but Bcl-2 expression was significantly increased in the 20 mg/L astragaloside-incubated adipose-derived stem cells + renal tubular epithelial cells group (P < 0.05). Results suggested that astragaloside-incubated human adipose-derived stem cells suppressed the apoptosis of renal tubular epithelial cells induced by cisplatin, which contributes to the early recovery of injured renal tubule. Its protective mechanism was probably associated with the secretion of insulin-like growth factor-1, inhibition of caspase-3 expression and upregulation of Bcl-2 levels.

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

全文链接：

Key words: stem cells, kidney tubules, epithelial cells, apoptosis

CLC Number:

R394.2

Wang Wei, Jiang Yan, Wang Wei-wei, Zhang Jin-yuan. Effects of adipose-derived stem cells cultured with astragaloside on cisplatin-induced apoptosis of renal tubular epithelial cells[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(28): 4498-4503.

Figures/Tables 4

References

[1]Huber JM,Tagwerker A,Heininger D,et al.The proteasome inhibitor bortezomib aggravates renal ischemia-reperfusion injury.Am J Physiol Renal Physiol.2009;297(2): 451-460.
[2]Jayati Sengupta. Pediatric AKI and management.Clinical Queries:Nephrology. 2013;2(3): 91-95.
[3]Luo J, Zhao X, Tan Z, et al. Mesenchymal-like progenitors derived from human embryonic stem cells promote recovery from acute kidney injury via paracrine actions.Cytotherapy. 2013;15(6):649-662.
[4]Liu N, Tian J, Cheng J, et al.Effect of erythropoietin on the migration of bone marrow-derived mesenchymal stem cells to the acute kidney injury microenvironment. Experimental Cell Res.2013;319(13):2019-2027.
[5]Imberti B, Morigi M, Tomasoni S, et al.Insulin-like growth factor-1 sustains stem cell mediated renal repair.J Am Soc Nephrol.2007;18:2921-2928.
[6]Chen Y, Qian H, Zhu W, et al.Hepatocyte growth factor modification promotes the amelioration effects of human umbilical cord mesenchymal stem cells on rat acute kidney injury.Stem Cells Dev.2011;20:103-113.
[7]Bi B, Guo J, Marlier A, et al.Erythropoietin expands a stromal cell population that can mediate renoprotection. Am J Physiol Renal Physiol.2008;295: 1017-1022.
[8]Zisa D, Shabbir A, Suzuki G, et al.Vascular endothelial growth factor (VEGF) as a key therapeutic trophic factor in bone marrow mesenchymal stem cell-mediated cardiac repair. Biochem Biophys Res Commun. 2009; 390(3): 834-838.
[9]Bi B, Schmitt R, Israilova M, et al. Stromal cells protect against acute tubular injury via an endocrine effect. J Am Soc Nephrol.2007;18(9):2486-2496.
[10]Eliopoulos N, Zhao J, Bouchentouf M, et al.Human marrow-derived mesenchymal stromal cells decrease cisplatin renotoxicity in vitro and in vivo and enhance survival of mice post-intraperitoneal injection.Am J Physiol Renal Physiol.2010;299(6):1288-1298.
[11]Zarjou A, Kim J, Traylor AM, et al. Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1.Am J Physiol Renal Physiol. 2011;300(1):254-262.
[12]Yen-Ta Chen,Cheuk-Kwan Sun,et al.Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction. J Transl Med. 2011;9:51.
[13]Liu Y, Yan X, Sun Z, et al. Flk-1+ adipose-derived mesenchymal stem cells differentiate into skeletal muscle satellite cells and ameliorate muscular dystrophy in mdx mice. Stem Cells Dev.2007;16(5):695-706.
[14]Li K, Han Q, Yan X, et al.Not a Process of Simple Vicariousness, the Differentiation of Human Adipose-Derived Mesenchymal Stem Cells to Renal Tubular Epithelial Cells Plays an Important Role in Acute Kidney Injury Repairing.Stem Cells Dev.2010;19(8):1267-1275.
[15]Yuan L, Wu MJ, Sun HY,et al.VEGF-modified human embryonic mesenchymal stem cell implantation enhances protection against cisplatin-induced acute kidney injury.Am J Physiol Renal Physiol.2011;300: 207-218.
[16]Mias C,Trouche E,Seguelas MH,et al.Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney. Stem Cells.2008;26:1749-1757.
[17]王葳,姜燕,王巍巍,等.黄芪甲苷对脂肪源性干细胞体外生物学行为的影响[J].中国药理学通报,2013,29(2):220-224.
[18]Kenchappa P, Yadav A, Singh G, et al. Rescue of TNF a-inhibited neuronal cells by IGF-1 involves Akt and c-JunN terminal kinases. J Neurosci Res.2004;76(4): 466-474.
[19]Bencomo E, Pérez R, Arteaga MF, et al. Apoptosis of cultured granulose-lutein cells is reduced by insulin-like growth factor 1 and may correlate with embryo fragmentation and pregnancy rate.Fertil Steril.2006;85(2): 474-480.
[20]Kang BP, Urbonas A, Baddoo A, et al. IGF-1 inhibits the mitochondrial apoptosis program in mesangial cells exposed to high glucose. Am J Physiol Renal Physio L. 2003;285(5): 1013-1024.
[21]方萍,邓叔华,刘柏炎.黄芪及其有效成分对干细胞影响的研究进展[J].中国中医药现代远程教育,2014,12(7):161-163.
[22]姜燕,王葳,李泽争,等.张金元芪甲苷孵育的脂肪源性干细胞对顺铂诱导的急性肾损伤小鼠的保护作用[J].中国中西医结合肾病杂志,2014,15(2):114-117,后插3-后插5页.
[23]王葳.黄芪甲苷孵育脂肪源性干细胞对顺铂诱导肾小管上皮细胞损伤的保护作用及机制研究[D].上海:上海中医药大学,2013.
[24]彭小娟,白海,王存邦,等.黄芪甲苷对人骨髓间充质干细胞体外增殖及细胞因子表达的影响[J].现代生物医学进展,2014,14(8): 1452-1455.
[25]王葳,姜燕,王巍巍,等.黄芪甲苷孵育脂肪源性干细胞对顺铂诱导的肾小管上皮细胞损伤的影响[J].中华肾脏病杂志,2013,29(7): 520-524.
[26]王莹,李文媛,刘贵波,等.黄芪皂甙Ⅳ联合ADSC对坐骨神经缺损后大鼠运动功能的修复作用[J].山东医药,2013,53(39):4-6.
[27]何文涓,袁志坚,张兰芳,等.黄芪注射液对兔脂肪来源的间充质干细胞体外增殖和细胞周期的影响[J].中国实验方剂学杂志,2011, 17(24):165-168.
[28]何文涓,何晓升,袁志坚,等.黄芪甲苷对兔脂肪来源的间充质干细胞体外增殖和细胞周期的影响[J].中国生化药物杂志,2011, 32(6):466-468.
[29]何文涓,张兰芳,袁志坚,等.黄芪多糖对兔脂肪来源的间充质干细胞体外增殖的影响[J].中国生化药物杂志,2011,32(5):387-389.