Data for: Effect of Source Animal Age upon Macrophage Response to Extracellular Matrix Biomaterials

Extracellular matrix biomaterials have been shown to promote constructive remodeling in many preclinical and clinical applications. This response has been associated with the promotion of a timely switch from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages. A previous study has shown that this beneficial response is lost when these biomaterials are derived from aged animals. This study examined the impact of small intestine submucosa (SIS) derived from 12, 26 and 52 week old pigs on the phenotype and function of bone marrow macrophages derived either from 2 or 18 month old mice. Results showed that 52 week old SIS promoted less iNOS in 2 month macrophages and Fizz1 expression in 2 and 18 month compared to 12 week SIS. Pro-inflammatory cytokine exposure to 52 week SIS-treated macrophages resulted in higher iNOS in 18 month macrophages and reduced MHC-II expression in 2 month macrophages, as well as reduced nitric oxide production in comparison to 12 week SIS. These results indicate that ECM derived from aged animals promotes an altered macrophage phenotype compared to young controls. This suggests that sourcing of ECM from young donors is important to preserve constructive remodeling outcomes of ECM biomaterials. Alteration of macrophage phenotype by aged ECM also raises the hypothesis that alterations in aged ECM may play a role in immune dysfunction in aged individuals.细胞外基质（extracellular matrix, ECM）生物材料已在众多临床前及临床应用中被证实可促进建设性组织重塑。该生物学效应与促炎型（pro-inflammatory, M1）巨噬细胞向抗炎型（anti-inflammatory, M2）巨噬细胞的适时极化转换密切相关。既往研究表明，当这类生物材料取自老年动物时，上述有益应答便会消失。本研究针对取自12周、26周及52周龄猪的小肠黏膜下层（small intestine submucosa, SIS），探究其对分别取自2月龄与18月龄小鼠的骨髓巨噬细胞表型及功能的影响。研究结果显示，与12周龄猪来源的SIS相比，52周龄猪来源的SIS可诱导2月龄巨噬细胞中诱导型一氧化氮合酶（inducible nitric oxide synthase, iNOS）的表达量更低，同时在2月龄与18月龄巨噬细胞中均可降低Fizz1基因的表达水平。经促炎细胞因子刺激后，相较于12周龄SIS处理组，52周龄SIS处理的18月龄巨噬细胞内iNOS表达水平更高，2月龄巨噬细胞的MHC-II（major histocompatibility complex class II）表达量降低，且一氧化氮生成量也随之减少。上述结果表明，与年轻供体来源的ECM相比，老年动物来源的ECM可诱导巨噬细胞表型发生改变。这提示我们，从年轻供体获取ECM对于维持ECM生物材料的建设性组织重塑效果至关重要。老年ECM对巨噬细胞表型的改变同时也提出了一项假说：老年ECM的结构改变可能在老年个体的免疫功能异常中发挥作用。