PXD048453

PXD048453 is an original dataset announced via ProteomeXchange.

Title	The Secretome of Macrophages Has a Differential Impact on Spinal Cord Injury Recovery According to the Polarization Protocol
Description	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. 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. 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. Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.
HostingRepository	PRIDE
AnnounceDate	2024-02-14
AnnouncementXML	Submission_2024-02-14_04:55:14.523.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vera Mendes
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-11 04:21:50	ID requested
⏵ 1	2024-02-14 04:55:14	announced

10.3389/FIMMU.2024.1354479;

submitter keyword: Spinal Cord Injury

Macrophages

Secretome

Proteomics, LC-MS/MS

Nuno Silva
contact affiliation	- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Portugal - ICVS/3B’s Associate Lab, PT Government Associated Lab, Portugal
contact email	nunosilva@med.uminho.pt
lab head
Vera Mendes
contact affiliation	Center for Neuroscience and Cell Biology, University of Coimbra
contact email	vera3m@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048453
     1. Label: PRIDE project
     2. Name: The Secretome of Macrophages Has a Differential Impact on Spinal Cord Injury Recovery According to the Polarization Protocol