College of Biomedical Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, People's Republic of China.
ACS Biomater Sci Eng. 2023 May 8;9(5):2426-2437. doi: 10.1021/acsbiomaterials.2c01538. Epub 2023 Apr 6.
Inefficient use and loss of exogenously implanted mesenchymal stem cells (MSCs) are major concerns in MSCs-based bone tissue engineering. It is a promising approach to overcome the above issues by recruiting and regulation of endogenous MSCs. However, there are few substances that can recruit MSCs effectively and specifically to the site of bone injury. In this study, we identified a phage clone (termed P11) with specific affinity for MSCs through phage display biopanning, and further investigated the effects of P11 on the cytological behavior of MSCs and macrophages. The results showed that P11 could bind MSCs specifically and promote the proliferation and migration of MSCs. Meanwhile, P11 could polarize macrophages to the M1 phenotype and significantly changed their morphology, which further enhanced the chemotaxis of MSCs. Additionally, RNA-seq results revealed that P11 could promote the secretion of osteogenesis-related markers in MSCs through the TPL2-MEK-ERK signaling pathway. Altogether, P11 has great potential to be used as growth factor alternatives in bone tissue engineering, with the advantages of cheaper and stable activity. Our study also advances the understanding of the effects of phages on macrophages and MSCs, and provides a new idea for the development in the field of phage-based tissue engineering.
外源性植入的间充质干细胞（MSCs）的低效利用和损失是基于 MSCs 的骨组织工程中的主要关注点。通过招募和调节内源性 MSCs 来克服上述问题是一种很有前途的方法。然而，目前很少有物质能够有效地、特异性地招募 MSCs 到骨损伤部位。在这项研究中，我们通过噬菌体展示生物淘选鉴定出一种对 MSCs 具有特异性亲和力的噬菌体克隆（命名为 P11），并进一步研究了 P11 对 MSCs 和巨噬细胞细胞行为的影响。结果表明，P11 可以特异性地结合 MSCs，并促进 MSCs 的增殖和迁移。同时，P11 可以将巨噬细胞极化为 M1 表型，并显著改变其形态，从而进一步增强 MSCs 的趋化性。此外，RNA-seq 结果表明，P11 可以通过 TPL2-MEK-ERK 信号通路促进 MSCs 中骨生成相关标志物的分泌。总之，P11 具有作为骨组织工程中生长因子替代物的巨大潜力，具有更便宜和稳定活性的优势。我们的研究还增进了对噬菌体对巨噬细胞和 MSCs 的影响的理解，为基于噬菌体的组织工程领域的发展提供了新的思路。
