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具有对骨髓和脾脏双重调节作用的新型碳点作为治疗脊髓损伤的潜在治疗候选物。

Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury.

作者信息

Li Junjin, Wang Hongda, Li Yuanquan, Wang Chunzhen, Feng Haiwen, Pang Yilin, Ren Jie, Li Chuanhao, Gao Erke, Zhang Dejing, Hu Dunxu, Zhao Pengtian, Ding Han, Fan Baoyou, Zhang Tao, Song Xiaomeng, Wei Zhijian, Ning Guangzhi, Li Yong-Qiang, Feng Shiqing

机构信息

Tianjin Key Laboratory of Spine and Spinal Cord, International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedics, International Chinese Musculoskeletal Research Society Collaborating Center for Spinal Cord Injury, Tianjin Medical University General Hospital, Tianjin, 300070, China.

Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan, 250100, China.

出版信息

Bioact Mater. 2024 Dec 11;45:534-550. doi: 10.1016/j.bioactmat.2024.11.032. eCollection 2025 Mar.

Abstract

Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site, exacerbating spinal cord damage. Simultaneously, bone marrow hematopoietic stem cells (HSCs) and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool. However, current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues, highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries. In this study, we designed, synthesized, and characterized novel Ejiao carbon dots (EJCDs) that inhibit myeloid cell proliferation and peripheral migration by promoting HSC self-renewal, and distinct differentiation into erythroid progenitors in vitro and in vivo. Additionally, EJCDs attenuate the immune response in the spleen, leukocytes' reservoir, following spinal cord injury by diminishing the local infiltration of monocytes and macrophages while promoting motor function recovery. These effects are mediated through the downregulation of CCAAT enhancer binding protein-β expression in the spleen and the upregulation of FZD4 protein expression in Lin Sca-1 c-kit cells (LSKs) within the bone marrow. Our findings demonstrate that EJCDs effectively reduce myeloid cell infiltration post-spinal cord injury and promote neurological recovery, making them promising therapeutic candidates for treating spinal cord injuries.

摘要

脊髓损伤会引发白细胞从外周循环向损伤部位的动员,从而加剧脊髓损伤。同时,骨髓造血干细胞(HSCs)和脾脏白细胞会迅速动员,以补充耗尽的外周血白细胞库。然而,目前针对脊髓损伤的治疗方法忽视了针对外周免疫器官和组织的干预措施,这凸显了开发能够有效调节外周免疫并治疗脊髓损伤的新型药物的必要性。在本研究中,我们设计、合成并表征了新型阿胶碳点(EJCDs),其通过促进HSC自我更新以及在体外和体内向红系祖细胞的独特分化,来抑制髓样细胞增殖和外周迁移。此外,EJCDs通过减少单核细胞和巨噬细胞的局部浸润,同时促进运动功能恢复,来减轻脊髓损伤后脾脏(白细胞储存库)中的免疫反应。这些作用是通过下调脾脏中CCAAT增强子结合蛋白-β的表达以及上调骨髓中Lin Sca-1 c-kit细胞(LSKs)中FZD4蛋白的表达来介导的。我们的研究结果表明,EJCDs能有效减少脊髓损伤后髓样细胞浸润并促进神经功能恢复,使其成为治疗脊髓损伤的有前景的治疗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/913e/11696655/420dac7a7e05/ga1.jpg

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