ArticlePloS one2020
The enhancement of CCL2 and CCL5 by human bone marrow-derived mesenchymal stem/stromal cells might contribute to inflammatory suppression and axonal extension after spinal cord injury.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- M2 polarization of macrophages: Manipulation of spinal cord injury repair.Neural regeneration research · 2026Article
- Combined Short-Chain Fatty Acids Induce an Anti-Inflammatory and Anti-Chemotactic Secretory Profile from 3T3-L1 Adipocytes in Normoxic and Hypoxic Environmental Conditions.International journal of molecular sciences · 2026Article
- The multidimensional signaling of ELANE: from congenital hematopoietic failure to immune microenvironment crosstalk and targeted interventions.Cell communication and signaling : CCS · 2026Review
- Dual CCR2/CCR5 Antagonism with Cenicriviroc Alleviates Nerve Injury-Induced Hypersensitivity and Prevents Morphine Tolerancevia Modulation of Neuroimmune Signaling.Cellular and molecular neurobiology · 2026Article
- Repurposing of Chemokine Antagonists for Combined Phase-Resolved Spinal Cord Injury Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reprogramming cellular senescence and aging clocks for advanced cancer immunotherapy.Molecular cancer · 2025Review
- iTRAQ proteomic analysis of exosomes derived from synovial fluid reveals disease patterns and potential biomarkers of Osteoarthritis.Journal of orthopaedic surgery and research · 2024Article
- CCL5 is essential for axonogenesis and neuronal restoration after brain injury.Journal of biomedical science · 2024Article
- Exacerbation of Hepatic Damage in Endothelial Aquaporin 1 Transgenic Mice after Experimental Heatstroke.Biomedicines · 2024Article
- Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential.International journal of molecular sciences · 2024Review
- Cell transplantation therapies for spinal cord injury focusing on bone marrow mesenchymal stem cells: Advances and challenges.World journal of stem cells · 2023Review
- Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review.Frontiers in immunology · 2023Review
- Stem cell-based therapy for human diseases.Signal transduction and targeted therapy · 2022Review
- Macrophage-based delivery of interleukin-13 improves functional and histopathological outcomes following spinal cord injury.Journal of neuroinflammation · 2022Article
- Mesenchymal Stem Cells in the Treatment of Human Spinal Cord Injury: The Effect on Individual Values of pNF-H, GFAP, S100 Proteins and Selected Growth Factors, Cytokines and Chemokines.Current issues in molecular biology · 2022Article
- Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury.Stem cell research & therapy · 2022Review
- Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration.Journal of neuroinflammation · 2021Review
- Current Concepts of Stem Cell Therapy for Chronic Spinal Cord Injury.International journal of molecular sciences · 2021Review
- Identification of Regeneration and Hub Genes and Pathways at Different Time Points after Spinal Cord Injury.Molecular neurobiology · 2021Article
- LINC01255 combined with BMI1 to regulate human mesenchymal stromal senescence and acute myeloid leukemia cell proliferation through repressing transcription of MCP-1.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) have shown potential in facilitating recovery from spinal cord injury (SCI) through communicating with microglia/macrophages (MG/MΦ). We here focused on chemokines as a candidate for the communication. Selected MG/MΦ-related chemokines were determined gene expression after SCI and further focused CCL2/CCR2 and CCL5/CCR5 to estimate role of the chemokines by hMSCs. Male C57/BL6 mice were subjected to spinal cord transection. Gene expression was assayed in the spinal cords following SCI for selected MG/MΦ-related chemokines and their receptors. hMSCs (5×105 cells) were then transplanted into parenchyma of the spinal cord, and the expressions of the Ccl2/Ccr2 and Ccl5/Ccr5 axes, inflammation, MG/MΦ-polarization, and axonal regeneration were evaluated to measure the influence of the hMSCs. Finally, mouse CCL5 was injected into the spinal cords. Acute increases in gene expression after SCI were observed for most chemokines, including Ccl2; chronic increases were observed for Ccl5. CCL2+-cells merged with NeuN+-neurons. CCR2+ immunoreactivity was principally observed in Ly-6G+/iNOS+-granulocytes on postoperative day (pod) 1, and CCL5+ and CCR5+ immunoreactivity overlapped with NeuN+-neurons and F4/80+-MG/MΦ on pod 14. The hMSC transplantation enhanced Ccl2 and Ccl5 and improved locomotor activity. The hMSC implantation did not alter the number of Ly-6G+/CCR2+ but decreased Il1, Elane, and Mpo on pod 3. Conversely, hMSC transplantation increased expression of Zc3h12a (encodes MCP-1-induced protein) on pod 14. Moreover, hMSC increased the Aif1, and two alternatively activated macrophage (AAM)-related genes, Arg1 and Chil3 (Ym1), as well as axonal regenerative markers, Dpysl2 and Gap43. Gene expression indicative of AAM polarization and axonal regeneration were partially recovered by CCL5 injection. These results suggest that hMSC implantation increases Ccl2 and Ccl5, improves locomotor activity, enhances MG/MΦ polarization to AAM, and increases the gene expression of axonal regenerative markers. These functions of hMSCs might be partially mediated by the CCL2/CCR2 and CCL5/CCR5 axes.
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