After spinal cord injury (SCI), there are complex pathological states in which the formation of scar tissues is a great obstacle to nerve repair. There are currently many potential treatments that can help to reduce the formation of glial scars. However, little attention has been paid to fibrous scarring. Astrocytes have neuroprotective effects on the central nervous system. Similar to other cells, they release small extracellular vesicles (sEVs). Astrocytes, pericytes, endothelial cells, and the basement membrane constitute the blood-spinal cord barrier. It can be seen that astrocytes are structurally closely related to pericytes that form fibrous scars. In this study, astrocyte-derived sEVs were injected into rats with SCI to observe the formation of fibrosis at the site of spinal cord injury. We found that astrocyte-derived sEVs can be ingested by pericytes in vitro and inhibit the proliferation and migration of pericytes. In vivo, astrocyte-derived sEVs could converge around the injury, promote tissue repair, and reduce fibrosis formation, thus promoting the recovery of limb function and improving walking ability. In conclusion, sEVs derived from astrocytes can reduce fibrosis and improve functional recovery after SCI, which provides a new possibility for the study of SCI.
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http://dx.doi.org/10.1016/j.intimp.2022.109322 | DOI Listing |
Brain Res
January 2024
Centro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago 7620001, Chile; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago 7620001, Chile. Electronic address:
Emerging evidence highlights the relevance of the protein post-translational modification by SUMO (Small Ubiquitin-like Modifier) in the central nervous system for modulating cognition and plasticity in health and disease. In these processes, astrocyte-to-neuron crosstalk mediated by extracellular vesicles (EVs) plays a yet poorly understood role. Small EVs (sEVs), including microvesicles and exosomes, contain a molecular cargo of lipids, proteins, and nucleic acids that define their biological effect on target cells.
View Article and Find Full Text PDFBiomedicines
November 2022
Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy.
All cells are capable of secreting extracellular vesicles (EVs), which are not a means to eliminate unneeded cellular compounds but represent a process to exchange material (nucleic acids, lipids and proteins) between different cells. This also happens in the brain, where EVs permit the crosstalk between neuronal and non-neuronal cells, functional to homeostatic processes or cellular responses to pathological stimuli. In brain tumors, EVs are responsible for the bidirectional crosstalk between glioblastoma cells and healthy cells, and among them, astrocytes, that assume a pro-tumoral or antitumoral role depending on the stage of the tumor progression.
View Article and Find Full Text PDFInt Immunopharmacol
December 2022
Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. Electronic address:
Exp Cell Res
October 2020
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address:
Astrocytes are major contributors of motor neuron (MN) degeneration in amyotrophic lateral sclerosis (ALS). We investigated whether regional and cell maturation differences influence ALS astrocyte malfunction. Spinal and cortical astrocytes from SOD1G93A (mSOD1) 7-day-old mice were cultured for 5 and 13 days in vitro (DIV).
View Article and Find Full Text PDFCells
April 2020
Centro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago 7550000, Chile.
In the last few decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP-tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) that are transferred into cultured hippocampal neurons.
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