TP53 缺失通过上调 NF-κB-IFN-β-MHC-Ia 信号促进骨肉瘤对 NK 细胞的抵抗
TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Safety study of allogeneic mesenchymal stem cell therapy in animal model.
Safety study of allogeneic mesenchymal stem cell therapy in animal model.
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静脉(IV)输注来自新生儿组织如脐带华通氏胶的间充质干细胞(MSCs)据报道对慢性疾病具有治疗作用。然而,这些细胞临床应用所必需的毒理学数据有限。
因此,本研究旨在确定大鼠静脉输注华通氏胶来源MSCs(WJ-MSCs)的安全性。十五只雄性Sprague-Dawley大鼠随机分为对照组或治疗组。每组分别接受等体积的生理盐水或WJ-MSC(10 10 6 cell/kg)。在为期12周的研究中,于第0、2、4、8和12周评估动物的物理、生化和血液学变化。急性毒性在第2周进行,亚慢性毒性在第12周进行。研究结束时,计算器官相对重量,并对肺、肝、脾和肾进行组织学检查。物理、血清生化和全血细胞计数的结果均显示组间无统计学显著差异。
然而,病理学评估报告所有组肺部均有轻微炎症,但仅在治疗组观察到明显的愈合和炎症消退。此外,与对照组相比,治疗组的组织学图像显示肺结构显著改善。
总之,WJ-MSC静脉给药在大鼠中是安全的。需要进一步研究以确定WJ-MSC在健康和疾病动物模型中的长期安全性。
Intravenous (IV) infusion of mesenchymal stem cells (MSCs) from nascent tissues like Wharton's Jelly of the umbilical cord is reported to offer therapeutic effects against chronic diseases.
However, toxicological data essential for the clinical application of these cells are limited.
Thus, this study aimed to determine the safety of IV infusion of Wharton's Jelly derived MSCs (WJ-MSCs) in rats. Fifteen male Sprague-Dawley rats were randomised into the control or treatment group. Each group received an equal volume of saline or WJ-MSC (10 10 6 cell/kg) respectively. The animals were evaluated for physical, biochemical and haematological changes at Week 0, 2, 4, 8 and 12 during the 12-week study.
Acute toxicity was performed during Week 2 and sub-chronic toxicity during Week 12. At the end of the study, the relative weight of organs was calculated and histology was performed for lung, liver, spleen and kidney. The findings from physical, serum biochemistry and complete blood count demonstrated no statistically significant differences between groups.
However, pathological evaluation reported minor inflammation in the lungs for all groups, but visible healing and resolution of inflammation were observed in the treatment group only.
Additionally, the histological images of the treatment group had significantly improved pulmonary structures compared to the control group. In summary, the IV administration of WJ-MSC was safe in the rats.
Further studies are needed to determine the long-term safety of the WJ-MSC in both healthy and diseased animal models.
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