Murayama Masatoshi, Chow Simon K, Lee Max L, Young Bill, Ergul Yasemin S, Shinohara Issei, Susuki Yosuke, Toya Masakazu, Gao Qi, Goodman Stuart B
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Department of Bioengineering, Stanford University School of Medicine, Stanford, California, USA.
Bone Joint Res. 2024 Sep 6;13(9):462-473. doi: 10.1302/2046-3758.139.BJR-2024-0122.R1.
Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes - the main cellular components in BMAC - interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.
骨再生和修复对于行走及生活质量至关重要。一般健康状况不佳、严重的医学合并症、慢性炎症和衰老等因素可导致骨折愈合延迟、不愈合以及持续性骨缺损。用于治疗骨病的生物工程策略通常涉及将自体骨髓抽吸浓缩物（BMAC）或间充质干细胞（MSC）与生物相容性支架进行移植。虽然BMAC显示出前景，但由于MSC浓度、活力以及免疫细胞组成的差异，其疗效存在变异性。了解巨噬细胞和淋巴细胞（BMAC中的主要细胞成分）与MSCs相互作用的机制，可能会提出增强骨愈合的新策略。巨噬细胞可极化为促炎性（M1）或抗炎性（M2）表型，并通过分泌细胞因子和其他因子影响细胞代谢和组织再生。T细胞，尤其是辅助性T1（Th1）和Th17细胞，促进炎症和破骨细胞生成，而Th2细胞和调节性T（Treg）细胞具有抗炎促重建作用，从而支持成骨作用。巨噬细胞、T细胞和MSCs之间的相互作用影响骨微环境并调节局部免疫反应。调控这些细胞的比例和相互作用为改变骨的局部再生能力提供了契机，这有可能改善临床疗效。
