Human umbilical cord mesenchymal stem cell-derived exosomes inhibit inflammation and fibrotic scar formation after intracerebral hemorrhage

• DOI: 10.1007/s11010-025-05259-2
• Publication Date: 2025-04-25T07:17:31Z
• Authors: Aobo Zhang; Zhanzhan Zhang; Rongge Liu; Zongmao Zhao; Liqiang Liu
• Keywords: Cord lining

Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-ex) have emerged as a promising alternative to whole-cell therapies due their minimal immunogenicity and tumorigenicity. Pentraxin 3 (PTX3) acts an inflammatory marker pattern recognition receptor, playing critical role in promoting tumor progression diseases. Fibrotic scars resulting from cerebral hemorrhage can impair motor sensory functions, leading poor prognosis. This study aimed investigate whether hUCMSC-ex regulate matrix metalloproteinase-3 (MMP3) expression via the PTX3/Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway, thereby inhibiting inflammation fibrotic scar formation following intracerebral ultimately recovery of nerve function. A stereotactic technique was used inject type IV collagenase (1 μL) into striatum rats, establishing animal model hemorrhagic stroke. Concurrently, were administered tail vein at dosage 200 μg. In vitro, primary astrocytes treated with subsequently stimulated Hemin (20 μmol/mL) create cellular hemorrhage. The levels PTX3, TLR4/NF-κB/MMP3 pathway proteins, factors, including necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), assessed both vivo vitro effects on response fibroblast migration. Neurological function rats evaluated days 1, 3, 5 using corner turn test, forelimb placement Longa score, Bederson score. Additionally, real-time PCR utilized measure PTX3 mRNA treatment hUCMSC-ex. inhibited MMP3 by downregulating protein TLR4, NF-κB/P65, p-P65. action resulted reduction pro-inflammatory cytokines TNF-α IL-1β while simultaneously increasing anti-inflammatory cytokine IL-10. Furthermore, suppressed response, prevented migration, decreased conditioned medium derived astrocytes. Importantly, improved behavioral performance (ICH). modulated through downregulation regulatory mechanism contributed decrease IL-1β, concurrently enhancing effectively reduced astrocyte-conditioned medium. Overall, significantly ICH.