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Open Access Review Article Issue
Stromal vascular fraction cell therapy: A promising therapeutic method for intracerebral hemorrhage
Brain Hemorrhages 2025, 6(3): 110-120
Published: 19 February 2025
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Intracerebral hemorrhage (ICH) is one of the most devastating and life-threatening forms of stroke, characterized by bleeding within the brain parenchyma. The condition is associated with a high mortality rate and significant long-term disabilities among survivors, underscoring the urgent need for innovative therapeutic strategies that go beyond managing symptoms to actively promote brain repair and functional recovery. Current treatment options are largely limited to supportive care, including surgical interventions to alleviate intracranial pressure and management of underlying risk factors such as hypertension. These approaches, however, fail to address the extensive neurological damage caused by ICH. Emerging evidence highlights the potential of stromal vascular fraction (SVF) cell therapy as a novel regenerative treatment for ICH. SVF, derived from adipose tissue through enzymatic digestion, is a heterogeneous mixture of cells, including mesenchymal stem cells (MSCs), endothelial cells, pericytes, immune cells, and progenitor cells. This cellular composition contributes synergistically to the repair and regeneration of damaged tissues. The mechanisms of action of SVF encompass inflammation modulation, neuroprotection, angiogenesis, and immunomodulation. MSCs within SVF release anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), reducing secondary injury caused by excessive inflammation. Endothelial cells and pericytes promote the formation of new blood vessels, restoring oxygen and nutrient supply to ischemic regions. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) further support neuronal survival and repair of neural circuits. Preclinical studies in animal models have consistently demonstrated the efficacy of SVF therapy, including reductions in brain edema, oxidative stress, and inflammatory cytokines, alongside improvements in angiogenesis, neuronal survival, and functional recovery. Early-phase clinical trials and case studies provide preliminary evidence of safety, feasibility, and potential therapeutic benefits in human patients with acute and chronic ICH. However, significant challenges remain, including the variability in SVF composition, optimal delivery methods, timing of intervention, and long-term safety considerations. This review comprehensively examines the biological properties of SVF, the mechanisms underlying its therapeutic effects, and the preclinical and clinical evidence supporting its use in ICH. Additionally, it explores future directions, including the development of standardized protocols, optimization of delivery techniques, integration with combination therapies, and the potential for personalized medicine approaches. As ongoing research and clinical trials refine these strategies, SVF therapy holds transformative potential to revolutionize ICH treatment by addressing its complex pathophysiology and improving patient outcomes. This novel approach not only promises to mitigate the immediate impacts of ICH but also offers hope for long-term recovery and enhanced quality of life for affected individuals.

Open Access Research Article Issue
Bioinformatics analysis of potential pathogenesis and risk genes of neuroinflammation-promoted brain injury in intracerebral hemorrhage
Brain Hemorrhages 2025, 6(1): 1-13
Published: 25 July 2024
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Objective

Spontaneous (non-traumatic) intracerebral hemorrhage (ICH) is one of the major causes of global death. The purpose of our bioinformatics analysis was to detect viable pathophysiological targets and small-molecule drug candidates and to identify the precise secondary mechanisms of brain injury in ICH.

Methods

The GSE24265 dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH. Online analysis tool GEO2R and Drug Susceptibility Assessment Module within the ACBI Bioinformation tool was used for data differential expression analysis. TargetScan, miRDB, and RNA22 were used to investigate the miRNAs regulating the DEGs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). DAVID is used to perform GO function enrichment analysis and KEGG pathway analysis of candidate target genes. Enrichment analysis was performed for delving the molecular mechanism of DEGs, and protein–protein interaction (PPI) networks and microRNA (miRNA)-messenger RNA (mRNA) networks were used to reveal the hub nodes and the related interaction relationships. Hub genes and miRNA-mRNA interaction of PPI network were identified by STRING version 12.0 online software and Cytoscape. Next, the DEGs were analyzed using the L1000CDS2 database to identify small-molecule compounds with potential therapeutic effects.

Results

A total of 325 upregulated genes and 103 downregulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to cytokine-cytokine receptor interaction and MAPK signaling pathway. A PPI network consisting of 188 nodes and 563 edges was constructed using STRING, and 27 hub genes were identified with Cytoscape software. The miRNA-mRNA network with high connectivity contained key 27 mRNAs (from C-C motif chemokine ligand 5 (CCL5), C-C motif chemokine ligand 8 (CCL8), …., to dishevelled-associated activator of morphogenesis 1 (DAAM1), and FRAT regulator of WNT signaling pathway 1 (FRAT1)) and 135 candidate miRNAs. These genes and miRNAs are closely related to secondary brain injury induced by ICH. In addition, a L1000CDS2 analysis of six small-molecule compounds revealed their therapeutic potential.

Conclusions

Our study explores the pathogenesis of brain tissue injury promoted by neuroinflammation in ICH and extends the clinical utility of its key genes. At the same time, we constructed a miRNA-mRNA network which may play crucial roles in the pathogenesis of ICH. In addition, we obtained six small molecule compounds that will have anti-inflammatory effects on ICH, including Geldanamycin, Dasatinib, BMS-345541, Saracatinib, and Afatinib.

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