Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution.
Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution.
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DOI：
10.1007/s00192-015-2831-5
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发表时间：
2016-02
影响因子：
1.8
通讯作者：
Hijaz A
中科院分区：
文献类型：
--
作者：
Sadeghi Z;Isariyawongse J;Kavran M;Izgi K;Marini G;Molter J;Daneshgari F;Flask CA;Caplan A;Hijaz A
我们评估了人间充质干细胞（hMSCs）在改善分娩创伤性损伤后尿失禁方面的潜在作用。
在阴道扩张（VD）后立即将人间充质干细胞经尿道周围或全身注射到大鼠体内（n = 90）。对照组包括非VD组（未受伤/未治疗，n = 15）、局部或全身注射生理盐水组（注射/对照，n = 90）以及皮肤成纤维细胞组（细胞治疗/对照，n = 90）。在4、10和14天后测量漏尿点压力（LPP）。对尿道进行形态测量评估。在另外几组VD和非VD大鼠中，分别使用人类Alu基因组重复序列染色、PKH26标记和荧光素酶表达标记来研究经尿道周围注射的人间充质干细胞的命运、生物分布和体内活力。
在第4天和第14天，生理盐水处理组和皮肤成纤维细胞处理组的对照大鼠的LPP低于非VD对照组（P <0.01）。在第4、10和14天，全身注射人间充质干细胞和经尿道周围注射人间充质干细胞治疗后的LPP与非VD对照组相当（P>0.05）。局部生理盐水对照组显示尿道组织广泛出血。在第4天和第14天，局部人间充质干细胞处理组与生理盐水处理组相比，结缔组织面积/尿道切片面积比例和血管密度分别更高。在第4、10和14天，在尿道中未观察到Alu染色阳性的细胞核。在2小时和24小时，在所有尿道中都发现了PKH26标记的细胞。生物发光研究显示，在人间充质干细胞注射后从第0天到第1天荧光素酶表达增加。
在VD模型中，人间充质干细胞恢复了控尿机制，具有即时和持续的效果，而生理盐水和皮肤成纤维细胞治疗则没有。人间充质干细胞在经尿道周围注射部位停留<7天。我们假设经尿道周围人间充质干细胞治疗可改善急性VD损伤后尿道组织的血管、结缔组织和出血状况。
We evaluated the potential role of human mesenchymal stem cells (hMSCs) in improvement of urinary continence following birth-trauma injury. Human MSCs were injected periurethrally or systemically into rats immediately after vaginal distention (VD) (n=90). Control groups were non-VD (uninjured/untreated, n=15), local or systemic saline (injection/control, n=90), and dermofibroblast (cell therapy/ control, n=90). Leak-point pressure (LPP) was measured 4, 10, and 14 days later. Urethras were morphometrically evaluated. In another sets of VD and non-VD rats, the fate of periurethrally injected hMSC, biodistribution, and in vivo viability was studied using human Alu genomic repeat staining, PKH26 labeling, and luciferase-expression labeling, respectively. Saline- and dermofibroblast-treated control rats demonstrated lower LPP than non-VD controls at days 4 and 14 (P <0.01). LPP after systemic hMSC and periurethral hMSC treatment were comparable with non-VD controls at 4, 10, and 14 days (P>0.05). Local saline controls demonstrated extensive urethral tissue bleeding. The connective tissue area/urethral section area proportion and vascular density were higher in the local hMSC- versus the saline-treated group at 4 and 14 days, respectively. No positive Alu-stained nuclei were observed in urethras at 4, 10, and 14 days. PKH26-labelled cells were found in all urethras at 2 and 24 h. Bioluminescence study showed increased luciferase expression from day 0 to 1 following hMSC injection. Human MSCs restored the continence mechanism with an immediate and sustained effect in the VD model, while saline and dermofibroblast therapy did not. Human MSCs remained at the site of periurethral injection for <7 days. We hypothesize that periurethral hMSC treatment improves vascular, connective tissue, and hemorrhage status of urethral tissues after acute VD injury.