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干细胞治疗阿霉素诱导的化疗脑的组织学实验研究。

Histological experimental study on the effect of stem cell therapy on adriamycin induced chemobrain.

机构信息

Department of Histology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Department of Histology, Faculty of Medicine, Beni-Suef University, Cairo, Egypt.

出版信息

Int J Stem Cells. 2013 Nov;6(2):104-12. doi: 10.15283/ijsc.2013.6.2.104.

Abstract

BACKGROUND AND OBJECTIVES

Negative consequences of chemotherapy on brain function were suggested and were addressed in animal models as the clinical phenomenon of chemobrain .It was postulated that adriamycin (ADR) induce changes in behaviour and in brain morphology. Human umbilical cord mesenchymal stem cells (HUCMSCs) could be induced to differentiate into neuron-like cells .The present study aimed at investigating the possible therapeutic effect of HUCMSC therapy on adriamycin induced chemobrain in rat.

METHODS AND RESULTS

Twenty five female albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg ADR. The rats were sacrificed two and four weeks following confirmation of brain damage. In stem cell therapy group, rats were injected with HUCMSCs following confirmation of brain damage and sacrificed two and four weeks after therapy. Brain sections were exposed to histological, histochemical, immunohistochemical and morphometric studies. In ADR group, multiple shrunken neurons exhibiting dark nuclei and surrounded by vacuoles were seen .In response to SC therapy ,multiple normal pyramidal nerve cells were noted. The area of shrunken nerve cells exhibiting dark nuclei, Prussion blue and CD105 positive cells were significantly different in ADR group in comparison to SC therapy group.

CONCLUSIONS

ADR induced progressive duration dependant cerebral degenerative changes. These changes were ameliorated following cord blood human mesenchymal stem cell therapy. A reciprocal relation was recorded between the extent of regeneration and the existence of undifferentiated mesenchymal stem cells.

摘要

背景与目的

化疗对大脑功能的负面影响在动物模型中被提出,并被称为“化疗脑”这一临床现象。有假设认为阿霉素(ADR)会引起行为和大脑形态的变化。人脐带间充质干细胞(HUCMSCs)可被诱导分化为神经元样细胞。本研究旨在探讨 HUCMSC 治疗对大鼠 ADR 诱导的化疗脑的可能治疗效果。

方法与结果

25 只雌性白化大鼠被分为对照组、ADR 组,ADR 组大鼠腹腔内(IP)单次注射 5mg/kg ADR。在确认脑损伤后两周和四周处死大鼠。在干细胞治疗组中,大鼠在确认脑损伤后接受 HUCMSC 注射,并在治疗后两周和四周处死。对脑切片进行组织学、组织化学、免疫组织化学和形态计量学研究。在 ADR 组中,可见多个萎缩的神经元,细胞核深染,周围有空泡。在 SC 治疗后,可见多个正常的锥体细胞。ADR 组中细胞核深染、普鲁士蓝和 CD105 阳性细胞的萎缩神经细胞面积明显小于 SC 治疗组。

结论

ADR 诱导了进行性、持续时间依赖性的大脑退行性变化。这些变化在脐带血人间充质干细胞治疗后得到改善。再生的程度与未分化的间充质干细胞的存在之间存在着相互关系。

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