{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Luca Guarrera"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-14942"],"description":["The severe and long-term consequences of traumatic brain injury (TBI) highlight the urgent need for effective neuroprotective therapies. Mesenchymal stromal cells (MSCs) show promise in TBI treatment through their secretome (conditioned media, CM). We previously identified a low-molecular-weight (<700Da) CM fraction with neuroprotective effects comparable to total CM after acute brain injury in vitro. Here we aimed at identifying key bioactive factors, reconstituting them into a synthetic cocktail (SYNT), and evaluating its efficacy in TBI models.  Metabolomic profiling identified three prostaglandins and kynurenine, which were used to create SYNT. The SYNT formulation reduced cell death, neuronal damage, and induced protective gene expression changes (NeuN and BDNF upregulation, Cd11b and IL6 downregulation) after TBI in vitro. In vivo, SYNT conferred similar long-term functional benefits as CM, improving sensorimotor function up to 6 months and memory preservation at 4 months compared to saline-treated animals, thought, only CM reduced contusion volume at 5 months. Both treatments modulated neuroinflammation, evidenced by reduced microglial activation and astrogliosis in the pericontusional tissue at 6 months.  These findings demonstrate the neuroprotective effects of MSC-secretome treatment in TBI and highlight prostaglandins and kynurenine as key mediators of this response. Our findings lay the groundwork for developing a standardized, cell-free therapeutic strategy for TBI based on MSC derivatives."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Nucleic Acid Extraction - Protocol: miRNeasy Mini Kit. Following the TruSeq Stranded Total RNA protocol (Illumina, San Diego, CA, USA), at least 500 ng of RNA whose RIN value was between 7 and 9, were used for RNA sequencing.","Sequencing - Illumina NEXTSEQ 500. RNA Sequencing (RNA-Seq) was run on a NextSeq 500 sequencer (Illumina) using a 1x75 high-output flow cell with 13 samples/run.","Library Construction - TruSeq Stranded Total RNA Sample Preparation Guide. Following the TruSeq Stranded Total RNA protocol (Illumina, San Diego, CA, USA), at least 500 ng of RNA whose RIN value was between 7 and 9, were used for RNA sequencing.","Sample Collection - Before library preparation, RNA concentration was evaluated through Qubit™ RNA High Sensitivity Assay Kit (Invitrogen, Walthman, MA, USA) while RNA quality was established using 4200 Tapestation (Agilent Technologies, Santa Clara, CA, USA)."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - Gene expression was quantified at the gene level by using the comprehensive annotations made available by Gencode. Samples were adjusted for library size and normalized with the variance stabilizing transformation (vst) in the R statistical environment using DESeq2 pipeline."],"omics_type":["Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["NextSeq 500"],"study_type":["RNA-seq of coding RNA"],"species":["Mus musculus"],"pubmed_authors":["Marco Bolis","Luca Guarrera"],"additional_accession":[]},"is_claimable":false,"name":"Mesenchymal stromal cell secretome and its key bioactive metabolites induce long-term neuroprotection after traumatic brain injury in mice","description":"The severe and long-term consequences of traumatic brain injury (TBI) highlight the urgent need for effective neuroprotective therapies. Mesenchymal stromal cells (MSCs) show promise in TBI treatment through their secretome (conditioned media, CM). We previously identified a low-molecular-weight (<700Da) CM fraction with neuroprotective effects comparable to total CM after acute brain injury in vitro. Here we aimed at identifying key bioactive factors, reconstituting them into a synthetic cocktail (SYNT), and evaluating its efficacy in TBI models.  Metabolomic profiling identified three prostaglandins and kynurenine, which were used to create SYNT. The SYNT formulation reduced cell death, neuronal damage, and induced protective gene expression changes (NeuN and BDNF upregulation, Cd11b and IL6 downregulation) after TBI in vitro. In vivo, SYNT conferred similar long-term functional benefits as CM, improving sensorimotor function up to 6 months and memory preservation at 4 months compared to saline-treated animals, thought, only CM reduced contusion volume at 5 months. Both treatments modulated neuroinflammation, evidenced by reduced microglial activation and astrogliosis in the pericontusional tissue at 6 months.  These findings demonstrate the neuroprotective effects of MSC-secretome treatment in TBI and highlight prostaglandins and kynurenine as key mediators of this response. Our findings lay the groundwork for developing a standardized, cell-free therapeutic strategy for TBI based on MSC derivatives.","dates":{"release":"2025-06-18T00:00:00Z","modification":"2025-03-18T13:39:33.911Z","creation":"2025-03-18T13:39:33.911Z"},"accession":"E-MTAB-14942","cross_references":{"ENA":["ERP170493"],"EFO":["EFO_0002944","EFO_0004170","EFO_0005518","EFO_0003816","EFO_0003738","EFO_0004184"]}}