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评估部分脱细胞化对气管冠状细胞和细胞外矩阵在呼吸道重建中的影响
Lumei Liu1, Jazmin Calyeca1, Sayali Dharmadhikari1
1Center for Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
概括
部分脱细胞化气管移植 (PDTG) 显示出气管替换的前景. 然而,在较大的动物模型中,部分脱细胞化 (PD) 具有负面影响,限制了临床转化.
科学领域:
- 生物材料科学 生物材料科学
- 再生医学是一种再生医学.
- 组织工程是组织工程.
背景情况:
- 部分脱细胞化气管移植 (PDTG) 提供了气管替代的潜力,支持新组织的形成而不会被排斥.
- 部分脱细胞化 (PD) 对细胞外基质 (ECM) 和细胞的影响尚不清楚,这阻碍了临床应用.
研究的目的:
- 在小鼠和子模型中量化PD对气管ECM和冠状细胞的影响.
- 通过评估PD对移植完整性和细胞组件的影响,评估PDTG在临床使用中的可翻译性.
主要方法:
- 在小鼠 (N=10/组) 中为期1个月的PDTG和同源气管移植 (STG) 的正位植入.
- 机械测试,冠状细胞活力和移植的蛋白质完整性分析.
- 在3个月和6个月的子 (N=3/时间点) 中进行儿科规模的PDTG测试,包括组织学,放射学和体外增殖分析.
主要成果:
- 在小鼠中的PD消除了上皮细胞,保持了状细胞的活力,并保持了机械性质和ECM完整性.
- 在小鼠中PDTG支持上皮质化和血管化.
- 与原生对照组相比,子PDTG显示辐射密度增加,体内较大胆小细胞/ECM损失,体外胆小细胞增殖减少.
结论:
- 虽然小鼠的PDTG表现出成功的新组织形成和保存了移植完整性,但子的人类PDTG表现出显著的状细胞和ECM损失.
- 这些发现表明,PD对冠状细胞和ECM的影响取决于模型,并对大规模的气道移植转化构成挑战.
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