Kang Dong Su, Song Young Min, Park Yeon Ji, Jeong Hyeon Jong, Hong Jung Joo, Seok Seung Hyeok, Na Yi Rang
Translational Immunology Lab, Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Immunology Core Facility, Department of Translational Research Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Front Immunol. 2025 Jul 21;16:1555695. doi: 10.3389/fimmu.2025.1555695. eCollection 2025.
Cellular therapy, including stem cell injections, has been proved to be therapeutic for patients with inflammatory bowel disease (IBDs), showing promising outcomes of disease progression. However, challenges of stem cell therapy remain, such as Crohn's disease with complex fistula, thus limiting its use and requiring another cellular therapy target for efficacy. Alternatively, macrophages have been reported to enhance recovery of damaged intestinal epithelial barriers during resolution of IBDs; thus, utilizing macrophage as a therapeutic strategy was hypothesized. In this study, we compared the regenerative capacity of wild-type and macrophages to validate the potential of genetically modified macrophages with low-inflammatory properties. Our findings demonstrate that macrophage transplantation ameliorates weight loss and shortening of colon in a mouse model of colitis. Imaging mass cytometry revealed that macrophages particularly increase the population of transit-amplifying cells. Cellular interaction analysis further identified a subset of fibroblast to be in proximity to these epithelial cell types. Collectively, this brief study suggests that phenotype-modified macrophage transplantation facilitates mucosal healing in IBDs, which is supporting evidence for potential cellular therapy in IBD patients.
细胞疗法,包括干细胞注射,已被证明对炎症性肠病(IBD)患者具有治疗作用,显示出疾病进展的良好前景。然而,干细胞疗法仍面临挑战,如伴有复杂瘘管的克罗恩病,因此限制了其应用,并需要另一种细胞治疗靶点来提高疗效。另外,据报道巨噬细胞在IBD消退过程中可促进受损肠上皮屏障的恢复;因此,有人提出将巨噬细胞作为一种治疗策略。在本研究中,我们比较了野生型和 巨噬细胞的再生能力,以验证具有低炎症特性的基因改造巨噬细胞的潜力。我们的研究结果表明,巨噬细胞移植可改善结肠炎小鼠模型的体重减轻和结肠缩短。成像质谱流式细胞术显示,巨噬细胞尤其增加了过渡扩增细胞的数量。细胞相互作用分析进一步确定了一部分成纤维细胞与这些上皮细胞类型相邻。总的来说,这项简短的研究表明,表型修饰的巨噬细胞移植有助于IBD的黏膜愈合,这为IBD患者潜在的细胞治疗提供了支持证据。