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超越脱细胞化:残留的线粒体DNA可以作为隐藏的损伤相关的分子模式

Elena V A van Hengel¹, Kuan Liu¹, Henk P Roest¹

¹Department of Surgery, Erasmus MC Transplant Institute, 3015 GD Rotterdam, The Netherlands.

Bioengineering (Basel, Switzerland)

|February 27, 2026

概括

线粒体DNA (mtDNA) 在组织脱细胞化后仍然存在,可能导致生物层中的免疫反应. 用HpaII内核酶处理支架有效地去除mtDNA,改善再生医学的生物相容性.

科学领域:

生物材料科学生物材料科学
免疫学免疫学免疫学
再生医学是一种再生医学.

背景情况:

组织脱细胞化为再生医学创造细胞外基质 (ECM) 生物支架.
脱细胞化有效地去除核DNA (nDNA),但残留量仍然存在.
脱细胞化后线粒体DNA (mtDNA) 的命运和免疫潜力尚不清楚.

研究的目的:

评估脱细胞化肝脏,胆道和血管支架中的残留mtDNA.
为了确定残留的mtDNA是否会在巨细胞中引发炎症反应.
评估减少生物层mtDNA的策略.

主要方法:

在脱细胞化的支架中定量残留DNA (nDNA和mtDNA).
在暴露于支架时评估巨细胞激活 (增殖,细胞因子产生).
用内核酶HpaII对支架进行处理,以降解mtDNA.

主要成果:

脱细胞化的支架显示总DNA减少,但相对mtDNA:nDNA比较高.
支架中的剩余mtDNA激活了巨细胞,增加了细胞增殖和细胞因子的释放.
HpaII治疗有效降解了mtDNA,并显著降低了巨细胞的激活.

结论:

线粒体DNA (mtDNA) 抵抗脱细胞化,并充当损伤相关分子模式 (DAMP).
生物支架中的剩余mtDNA可以引起炎症反应,影响免疫不相容性.
针对性去除mtDNA,例如使用HpaII,对于提高生物医学应用中脱细胞化生物支架的安全性和有效性至关重要.

关键词:

与损伤相关的分子模式 (DAMP)脱细胞化脱细胞化细胞外矩阵 (ECM) 是一个细胞外矩阵.天生的免疫反应.巨细胞是什么?巨细胞是什么?线粒体DNA是线粒体DNA的组成部分.核的 DNA 核的 DNA 核的 DNA 限制酶消化酶的消化组织工程是组织工程.

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