McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, 15219 PA, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, 15219 PA, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, 15219 PA, USA; DoD-VA Extremity Trauma & Amputation Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD 20889, USA.
Biomaterials. 2015 Apr;46:131-40. doi: 10.1016/j.biomaterials.2014.12.044. Epub 2015 Jan 24.
Extracellular matrix (ECM) derived from a variety of source tissues has been successfully used to facilitate tissue reconstruction. The recent development of solubilized forms of ECM advances the therapeutic potential of these biomaterials. Isolated, soluble components of ECM and matricryptic peptides have been shown to bias macrophages toward a regulatory and constructive (M2-like) phenotype. However, the majority of studies described thus far have utilized anatomically and morphologically similar gastrointestinal derived ECMs (small intestine, esophagus, urinary bladder, etc.) and a small subset of macrophage markers (CD206, CD86, CCR7) to describe them. The present study evaluated the effect of solubilized ECM derived from molecularly diverse source tissues (brain and urinary bladder) upon primary macrophage phenotype and function. Results showed that solubilized urinary bladder ECM (U-ECM) up-regulated macrophage PGE2 secretion and suppressed traditional pro-inflammatory factor secretion, consistent with an M2-like phenotype. The hyaluronic acid (HA) component in solubilized U-ECM played an important role in mediating this response. Brain ECM (B-ECM) elicited a pro-inflammatory (M1-like) macrophage response and contained almost no HA. These findings suggest that the molecular composition of the source tissue ECM plays an important role in influencing macrophage function and phenotype.
细胞外基质（ECM）来源于多种组织来源，已成功用于促进组织重建。最近可溶形式的 ECM 的发展推进了这些生物材料的治疗潜力。已经表明 ECM 的分离的、可溶的成分和基质cryptic 肽使巨噬细胞向调节和建设性（M2 样）表型倾斜。然而，迄今为止描述的大多数研究都利用解剖学和形态学上相似的胃肠道来源的 ECM（小肠、食管、膀胱等）和一小部分巨噬细胞标志物（CD206、CD86、CCR7）来描述它们。本研究评估了源自分子上多样化的组织（脑和膀胱）的可溶 ECM 对原代巨噬细胞表型和功能的影响。结果表明，可溶膀胱 ECM（U-ECM）上调巨噬细胞 PGE2 分泌并抑制传统的促炎因子分泌，与 M2 样表型一致。可溶 U-ECM 中的透明质酸（HA）成分在介导这种反应中起重要作用。脑 ECM（B-ECM）引起促炎（M1 样）巨噬细胞反应，几乎不含 HA。这些发现表明，来源组织 ECM 的分子组成在影响巨噬细胞功能和表型方面起着重要作用。
