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间充质干细胞限制慢性放射性膀胱炎中的血管与上皮损伤并恢复尿路上皮的不通透性

英文原题:Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis.

查看英文原题

Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis.

PubMed 2023/01/11(内容时间) Stem Cell Res Ther Q1 · IF 7.8(JCR 2025)

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研究概要

这些结果支持 MSCs 有助于限制放射性膀胱炎慢性期的进展。MSC 治疗可能为所有对常规治疗耐药的慢性放射性膀胱炎患者带来真正的希望。

研究思路结论见上方概要

细胞治疗似乎是一种创新的治疗选择,间充质干细胞(MSCs)已被证明对间质性和出血性膀胱炎有效。然而,MSCs对慢性放射性膀胱炎(CRC)的作用仍有待证实。本研究旨在建立CRC大鼠模型,并评估MSCs的疗效及其作用方式。

在雌性Sprague-Dawley大鼠中,通过断层扫描引导的双束对整个膀胱进行单次局部照射诱导CRC。使用20-80 Gy的剂量范围,照射后随访3-12个月,以表征大鼠放射性膀胱炎的剂量效应和动力学。对于治疗,保留40 Gy的剂量,并且为了增强MSC的效果,从脂肪组织中分离MSC。扩增后,在慢性前期经静脉注射。每两周给予三次5百万MSC的注射。照射后随访12个月。

我们观察到,血尿的强度和频率与照射剂量成正比,阈值为40 Gy,并且在照射后100天开始出现出血。MSCs减轻了血管损伤以及膀胱上皮的损伤。

展开英文摘要原文

Cellular therapy seems to be an innovative therapeutic alternative for which mesenchymal stem cells (MSCs) have been shown to be effective for interstitial and hemorrhagic cystitis. However, the action of MSCs on chronic radiation cystitis (CRC) remains to be demonstrated. The aim of this study was to set up a rat model of CRC and to evaluate the efficacy of MSCs and their mode of action.

CRC was induced by single-dose localized irradiation of the whole bladder using two beams guided by tomography in female Sprague-Dawley rat. A dose range of 20-80 Gy with follow-up 3-12 months after irradiation was used to characterize the dose effect and the kinetics of radiation cystitis in rats. For the treatment, the dose of 40 Gy was retained, and in order to potentiate the effect of the MSCs, MSCs were isolated from adipose tissue. After expansion, they were injected intravenously during the pre-chronic phase. Three injections of 5 million MSCs were administered every fortnight. Follow-up was performed for 12 months after irradiation.

We observed that the intensity and frequency of hematuria are proportional to the irradiation dose, with a threshold at 40 Gy and the appearance of bleeding from 100 days post-irradiation. The MSCs reduced vascular damage as well as damage to the bladder epithelium.

These results are in favor of MSCs acting to limit progression of the chronic phase of radiation cystitis. MSC treatment may afford real hope for all patients suffering from chronic radiation cystitis resistant to conventional treatments.

论文信息

作者
Brossard C、Pouliet AL、Lefranc AC、Benadjaoud M、Dos Santos M、Demarquay C、Buard V、Benderitter M
第一作者单位
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SERAMed/LRMed, 92260, Fontenay-aux-Roses, France.France
通讯作者单位
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SERAMed/LRMed, 92260, Fontenay-aux-Roses, France. alain.chapel@irsn.fr.France
文献类型
非美国政府资助研究
期刊
Stem cell research & therapy2023 Jan 11
原文标识
PubMed 36627674 · DOI 10.1186/s13287-022-03230-2