Luo Haiyun, Liu Wenjing, Zhou Yachuan, Jiang Xiao, Liu Yeungyeung, Yang Qin, Shao Longquan
Department of Endodontics, Stomatological Hospital, Southern Medical University, 366 Jiangnan Avenue South, Guangzhou 510280, China.
Department of Prosthodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.
Regen Biomater. 2021 Aug 17;8(6):rbab049. doi: 10.1093/rb/rbab049. eCollection 2021 Oct.
Concentrated growth factor (CGF) is a promising regenerative material that serves as a scaffold and adjunct growth factor for tissue engineering. The host immune response, particularly macrophage activity, plays a critical role in injury repair and tissue regeneration. However, the biological effect of CGF on the immune response is not clear. To enrich the theoretical groundwork for clinical application, the present study examined the immunoregulatory role of CGF in macrophage functional activities . The CGF scaffold appeared as a dense fibrin network with multiple embedded leukocytes and platelets, and it was biocompatible with macrophages. Concentrated bioactive factors in the CGF extract enhanced THP-1 monocyte recruitment and promoted the maturation of suspended monocytes into adherent macrophages. CGF extract also promoted THP-1 macrophage polarization toward the M2 phenotype with upregulated CD163 expression, as detected by cell morphology and surface marker expression. A cytokine antibody array showed that CGF extract exerted a regulatory effect on macrophage functional activities by reducing secretion of the inflammatory factor interleukin-1β while inducing expression of the chemokine regulated on activation, normal T cell expressed and secreted. Mechanistically, the AKT signaling pathway was activated, and an AKT inhibitor partially suppressed the immunomodulatory effect of CGF. Our findings reveal that CGF induces a favorable immune response mediated by macrophages, which represents a promising strategy for functional tissue regeneration.
浓缩生长因子（CGF）是一种很有前景的再生材料，可作为组织工程的支架和辅助生长因子。宿主免疫反应，尤其是巨噬细胞活性，在损伤修复和组织再生中起着关键作用。然而，CGF对免疫反应的生物学作用尚不清楚。为丰富临床应用的理论基础，本研究探讨了CGF在巨噬细胞功能活动中的免疫调节作用。CGF支架呈现为一个密集的纤维蛋白网络，其中嵌入了多个白细胞和血小板，并且它与巨噬细胞具有生物相容性。CGF提取物中的浓缩生物活性因子增强了THP-1单核细胞的募集，并促进悬浮单核细胞成熟为贴壁巨噬细胞。通过细胞形态学和表面标志物表达检测发现，CGF提取物还促进THP-1巨噬细胞向M2表型极化，CD163表达上调。细胞因子抗体阵列显示，CGF提取物通过减少炎症因子白细胞介素-1β的分泌，同时诱导趋化因子“活化调节正常T细胞表达和分泌因子”的表达，对巨噬细胞功能活动发挥调节作用。机制上，AKT信号通路被激活，AKT抑制剂部分抑制了CGF的免疫调节作用。我们的研究结果表明，CGF诱导由巨噬细胞介导的良好免疫反应，这代表了一种用于功能性组织再生的有前景的策略。
