Modulation of the inflammatory response to decellularized collagen matrix for cartilage regeneration
Modulation of the inflammatory response to decellularized collagen matrix for cartilage regeneration
复制标题
脱细胞胶原基质对软骨再生炎症反应的调节作用
DOI：
10.1002/jbm.a.37349
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发表时间：
2021-12-29
影响因子：
4.9
通讯作者：
Rotter, Nicole
中科院分区：
文献类型：
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作者：
Gvaramia, David;Kern, Johann;Rotter, Nicole
脱细胞细胞外基质（DECM）是组织工程中最常用的材料之一，因为它们具有细胞指导性、生物降解性和可接近性。特别是在软骨中，天然II型胶原基质可以是为软骨干细胞和祖细胞（CSPC）提供必要线索和支持的有希望的手段。然而，移植DECM的有效重塑在很大程度上取决于宿主免疫反应，其中巨噬细胞在协调炎症和再生过程中发挥着核心作用。在这里，我们评估了人原代巨噬细胞对软骨DECM的反应。我们的研究结果表明，异种胶原蛋白基质可以引起混合反应，在人类巨噬细胞，其中炎症反应（M1）和激活重塑（M2）型的巨噬细胞都存在。此外，我们证明了巨噬细胞反应对人CSPC迁移能力的抑制作用。我们进一步表明，巨噬细胞对软骨DECM的炎症反应，以及由此产生的对CSPC迁移的抑制作用，可以被白细胞介素-4（IL-4）减弱。最后，我们证明了IL-4可以有效地结合基质，从而通过减少炎症反应和诱导M2表型来调节巨噬细胞反应。
Decellularized extracellular matrices (DECM) are among the most common types of materials used in tissue engineering due to their cell instructive properties, biodegradability, and accessibility. Particularly in cartilage, a natural collagen type II matrix can be a promising means to provide the necessary cues and support for chondrogenic stem and progenitor cells (CSPCs). However, efficient remodeling of the transplanted DECM is largely dependent on the host immune response, with macrophages playing the central role in orchestrating both inflammatory and regenerative processes. Here we assessed the reaction of human primary macrophages to the cartilage DECM. Our findings show that the xenogeneic collagen matrix can elicit a mixed response in human macrophages, whereby the inflammatory response (M1) and the activation of remodeling (M2) type of macrophages are both present. Additionally, we demonstrate the inhibitory effect of macrophage response on the migratory capacity of human CSPCs. We further show that the inflammatory reaction of macrophages to the cartilage DECM, as well as the resulting inhibitory effects on CSPC migration, can be attenuated by interleukin-4 (IL-4). Finally, we demonstrate that IL-4 can effectively bind the matrix, thereby modulating macrophage response by reducing the inflammatory reaction and inducing the M2 phenotype.