ArticleFrontiers in immunology2024
The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 7 citations in OpenAlex.
- Transplantation of LPS, IL-4, and TGF-β-induced reparative-biased macrophages promotes early motor functional recovery after spinal cord injury in rats.Journal of orthopaedic translation · 2026Article
- The Fidelity Paradox in Spinal Cord Injury: Reframing Biomechanical Mimicry and Neurobiological Relevance for Clinical Translation.CNS neuroscience & therapeutics · 2026Review
- Targeting the glial-fibrotic scar microenvironment after spinal cord injury: From integrated protection to systematic regulation of regenerative balance.Journal of orthopaedic translation · 2026Review
- Surface marker-defined functional subpopulations of mesenchymal stromal cells: mechanisms, applications, and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Conditioned Media from Mechanically Stimulated Macrophages Upregulate Osteogenic Genes in Human Mesenchymal Stromal Cells.Advanced healthcare materials · 2025Article
- Proinflammatory macrophage secretome enhances temozolomide sensitivity in glioblastoma via pSTAT3-mediated downregulation of DNA repair enzymes.Scientific reports · 2025Article
- Modeling Spinal Cord Injury in a Dish with Hyperosmotic Stress: Population-Specific Effects and the Modulatory Role of Mesenchymal Stromal Cell Secretome.International journal of molecular sciences · 2025Article
- Development and application of a novel multi-channel in vitro electrical stimulator for cellular research.BMC biomedical engineering · 2025Article
- Mapping the Landscape of Mesenchymal Stem Cell-Derived Extracellular Vesicles: From Bench to Bedside.Stem cells international · 2025Article
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Authors and funding
24 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. Methods: In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. Results: We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Discussion: Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.