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

脾脏 脊髓损伤 骨髓 材料科学 生物医学工程 脊髓 医学 病理 免疫学 精神科
作者
Junjin Li,Hongda Wang,Yuanquan Li,Yuanquan Li,Chunzhen Wang,Haiwen Feng,Yilin Pang,Jie Ren,Chuanhao Li,Enjun Gao,D. B. Zhang,Dehong Hu,Pengtian Zhao,Han‐Fei Ding,Baoyou Fan,Tao Zhang,Xiaomeng Song,Zhijian Wei,Guangzhi Ning,Yongqiang Li
出处
期刊:Bioactive Materials [Elsevier BV]
卷期号:45: 534-550 被引量:5
标识
DOI:10.1016/j.bioactmat.2024.11.032
摘要

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. • EJCDs can enhance HSCs self-renewal and erythroid differentiation. • EJCDs inhibit myeloid cell proliferation and peripheral migration. • EJCDs diminish local infiltration of monocytes and macrophages. • EJCDs promote motor function and neurological recovery. • EJCDs regulate immune response through dual-regulation of peripheral immune organs.
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