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

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. Howev...

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Main Authors: Junjin Li, Hongda Wang, Yuanquan Li, Chunzhen Wang, Haiwen Feng, Yilin Pang, Jie Ren, Chuanhao Li, Erke Gao, Dejing Zhang, Dunxu Hu, Pengtian Zhao, Han Ding, Baoyou Fan, Tao Zhang, Xiaomeng Song, Zhijian Wei, Guangzhi Ning, Yong-Qiang Li, Shiqing Feng
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-03-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24005243
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author Junjin Li
Hongda Wang
Yuanquan Li
Chunzhen Wang
Haiwen Feng
Yilin Pang
Jie Ren
Chuanhao Li
Erke Gao
Dejing Zhang
Dunxu Hu
Pengtian Zhao
Han Ding
Baoyou Fan
Tao Zhang
Xiaomeng Song
Zhijian Wei
Guangzhi Ning
Yong-Qiang Li
Shiqing Feng
author_facet Junjin Li
Hongda Wang
Yuanquan Li
Chunzhen Wang
Haiwen Feng
Yilin Pang
Jie Ren
Chuanhao Li
Erke Gao
Dejing Zhang
Dunxu Hu
Pengtian Zhao
Han Ding
Baoyou Fan
Tao Zhang
Xiaomeng Song
Zhijian Wei
Guangzhi Ning
Yong-Qiang Li
Shiqing Feng
author_sort Junjin Li
collection DOAJ
description 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.
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spelling doaj-art-bcd41cf8faa04cc6a1209f462332b06f2025-01-26T05:04:25ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-03-0145534550Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injuryJunjin Li0Hongda Wang1Yuanquan Li2Chunzhen Wang3Haiwen Feng4Yilin Pang5Jie Ren6Chuanhao Li7Erke Gao8Dejing Zhang9Dunxu Hu10Pengtian Zhao11Han Ding12Baoyou Fan13Tao Zhang14Xiaomeng Song15Zhijian Wei16Guangzhi Ning17Yong-Qiang Li18Shiqing Feng19Tianjin 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, ChinaTianjin 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, ChinaTianjin 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, ChinaInstitute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan, 250100, ChinaTianjin 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, ChinaOrthopedic Research Center of Shandong University and Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, 250012, ChinaTianjin 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, ChinaTianjin 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, ChinaThe First Central Clinical School, Tianjin Medical University, Tianjin, 300070, ChinaThe First Central Clinical School, Tianjin Medical University, Tianjin, 300070, ChinaThe First Central Clinical School, Tianjin Medical University, Tianjin, 300070, ChinaThe First Central Clinical School, Tianjin Medical University, Tianjin, 300070, ChinaTianjin 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, ChinaTianjin 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, ChinaDepartment of Orthopaedics, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Tianqiao District, Jinan, 250033, ChinaTianjin 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, ChinaTianjin 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; Orthopedic Research Center of Shandong University and Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China; Corresponding author. 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.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; Corresponding author. 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; Corresponding author. Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan, 250100, China.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; Orthopedic Research Center of Shandong University and Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China; Department of Orthopaedics, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Tianqiao District, Jinan, 250033, China; Corresponding author. 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.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.http://www.sciencedirect.com/science/article/pii/S2452199X24005243Spinal cord injuryCarbon dotsHematopoietic stem cellsBone marrowSpleen
spellingShingle Junjin Li
Hongda Wang
Yuanquan Li
Chunzhen Wang
Haiwen Feng
Yilin Pang
Jie Ren
Chuanhao Li
Erke Gao
Dejing Zhang
Dunxu Hu
Pengtian Zhao
Han Ding
Baoyou Fan
Tao Zhang
Xiaomeng Song
Zhijian Wei
Guangzhi Ning
Yong-Qiang Li
Shiqing Feng
Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury
Bioactive Materials
Spinal cord injury
Carbon dots
Hematopoietic stem cells
Bone marrow
Spleen
title Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury
title_full Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury
title_fullStr Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury
title_full_unstemmed Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury
title_short Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury
title_sort novel carbon dots with dual modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury
topic Spinal cord injury
Carbon dots
Hematopoietic stem cells
Bone marrow
Spleen
url http://www.sciencedirect.com/science/article/pii/S2452199X24005243
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