Human unrestricted somatic stem cell administration fails to protect nude mice from cisplatin-induced acute kidney injury.

Nephron Experimental Nephrology Pub Date : 2013-01-01 Epub Date: 2013-08-01 DOI:10.1159/000353233
Yousof Gheisari, Naser Ahmadbeigi, Seyed Hamid Aghaee-Bakhtiari, Seyed Mahdi Nassiri, Saeid Amanpour, Kayhan Azadmanesh, Athena Hajarizadeh, Zahra Mobarra, Masoud Soleimani
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引用次数: 3

Abstract

Background: Kidney failure is a debilitating disorder with limited treatment options. The kidney-protective effects of stem cells have been vastly investigated and promising results have been achieved with various sources of stem cells. However, in spite of beneficial effects on other disease models, the renoprotective potential of human cord blood-derived unrestricted somatic stem cells (USSC) has not been examined so far.

Methods: In the present study, acute kidney failure was induced in female nude mice and the effect of USSC transplantation on kidney function and structure was assessed. Furthermore, the expression of some cytokine genes was examined by real-time PCR. Homing of the transplanted cells into kidneys was assessed by flow cytometry, immunohistochemistry, and real-time PCR.

Results: USSC-conditioned medium did not attenuate the in vitro nephrotoxic effects of cisplatin. Transplantation of USSC to nude mice did not protect kidney function and was associated with worsened kidney structural damage. USSC transplantation was also associated with a decline in the renal expression of VEGF-A gene. In spite of these effects, the transplanted cells could not be detected in the kidneys by any of the exploited methods and they were mainly entrapped in the lungs.

Conclusion: These data indicate that USSC are not suitable for cell therapy in the setting of acute kidney injury. Also, this study shows that these stem cells are able to affect damaged kidneys even if they are not homed there.

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人类不受限制的体细胞干细胞给药不能保护裸鼠免受顺铂诱导的急性肾损伤。
背景:肾衰竭是一种使人衰弱的疾病,治疗选择有限。干细胞的肾保护作用已被广泛研究,各种来源的干细胞已取得了令人鼓舞的结果。然而,尽管对其他疾病模型有有益作用,但人类脐带血来源的非限制性体细胞干细胞(USSC)的肾保护潜力迄今尚未得到检验。方法:本研究采用雌性裸鼠诱导急性肾衰竭,观察USSC移植对肾脏功能和结构的影响。实时荧光定量PCR检测部分细胞因子基因的表达。通过流式细胞术、免疫组织化学和实时PCR评估移植细胞在肾脏中的归巢情况。结果:ussc条件培养基没有减弱顺铂的体外肾毒性作用。裸鼠移植USSC不能保护肾脏功能,并伴有肾脏结构损伤加重。USSC移植也与肾脏VEGF-A基因表达的下降有关。尽管有这些效果,移植的细胞在肾脏中无法被检测到,它们主要被困在肺部。结论:这些数据表明USSC不适合用于急性肾损伤的细胞治疗。此外,这项研究表明,这些干细胞能够影响受损的肾脏,即使它们不在那里。
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Nephron Experimental Nephrology
Nephron Experimental Nephrology 医学-泌尿学与肾脏学
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