Human adipose and umbilical cord mesenchymal stem cell-derived extracellular vesicles mitigate photoaging via TIMP1/Notch1

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 30, 2024

Abstract UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant potential various diseases. Given extracellular vesicles (EV) can deliver diverse cargo recipient elicit similar effects, we investigated the roles underlying mechanisms both adipose-derived MSC-derived EV (AMSC-EV) umbilical cord-derived (HUMSC-EV) in photoaging. Our findings vivo, treatment with AMSC-EV HUMSC-EV resulted improvements wrinkles hydration while also mitigating inflammation thickness alterations epidermis dermis. Additionally, vitro studies using human keratinocytes (HaCaTs), dermal fibroblast (HDFs), T-Skin models revealed attenuated senescence, reduced levels reactive oxygen species (ROS) alleviated induced by UVB. Furthermore, enhanced cell viability migration capacity promoted matrix (ECM) remodeling dermis photoaged models. Mechanistically, proteomics results showed TIMP1 was highly expressed could exert effects as MSC-EV. In addition, found inhibit Notch1 downstream targets Hes1, P16, P21, P53. Collectively, our data suggests attenuate through TIMP1/Notch1.

Language: Английский

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Lipid Nanoparticle-Based Delivery System─A Competing Place for mRNA Vaccines

ACS Omega, Journal Year: 2024, Volume and Issue: 9(6), P. 6219 - 6234

Published: Jan. 30, 2024

mRNA, as one of the foci biomedical research in past decade, has become a candidate vaccine solution for various infectious diseases and tumors regenerative medicine immunotherapy due to its high efficiency, safety, effectiveness. A stable effective delivery system is needed protect mRNAs from nuclease degradation while also enhancing immunogenicity. The success mRNA lipid nanoparticles treating COVID-19, certain extent, marks milestone vaccines promotes further on systems. Here, we explore systems, especially (LNPs), considering current status, prospects, challenges nanoparticles, other

Language: Английский

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Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: March 19, 2024

Abstract Background Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and tissue damage, frequently causing rapid failure long-term complications. The microRNA let-7a-5p involved in the progression of injury, inflammation, fibrosis regulating immune cell activation cytokine production. This study aims to use an innovative cellular electroporation platform generate extracellular vesicles (EVs) carring (EV- ) derived from transfected Wharton’s jelly-mesenchymal stem cells (WJ-MSCs) as potential gene therapy for ALI. Methods A nanoporation (CNP) method was used induce production release EV- WJ-MSCs with relevant plasmid DNA. conditioned medium were isolated using tangential flow filtration (TFF) system. EV characterization followed minimal consensus guidelines outlined International Society Extracellular Vesicles. We conducted thorough set therapeutic assessments, including antifibrotic effects transforming growth factor beta (TGF-β)-induced model, modulation on macrophage polarization, influence rat model hyperoxia-induced Results CNP significantly increased secretion WJ-MSCs, encapsulated engineered EVs markedly higher than that untreated WJ-MSCs. These did not proliferation effectively mitigated TGF-β-induced fibrotic phenotype downregulating SMAD2/3 phosphorylation LL29 cells. Furthermore, regulated M2-like inflammatory microenvironment induced interleukin (IL)-10 secretion, demonstrating their modulatory effect inflammation. Administering slightly improved function expression plasma ALI model. In comparison, reduced infiltration collagen deposition while increasing IL-10 expression, substantial improvement function. Conclusion reveals stimulate transfect could abundance -enriched EVs, which underscores countering responses, activation, injury. results provide avenues developing approaches more effective interventions

Language: Английский

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Charge‐Reversed Exosomes for Targeted Gene Delivery to Cartilage for Osteoarthritis Treatment

Small Methods, Journal Year: 2024, Volume and Issue: 8(9)

Published: April 12, 2024

Abstract Gene therapy has the potential to facilitate targeted expression of therapeutic proteins promote cartilage regeneration in osteoarthritis (OA). The dense, avascular, aggrecan‐glycosaminoglycan (GAG) rich negatively charged cartilage, however, hinders their transport reach chondrocytes effective doses. While viral vector mediated gene delivery shown promise, concerns over immunogenicity and tumorigenic side‐effects persist. To address these issues, this study develops surface‐modified cartilage‐targeting exosomes as non‐viral carriers for therapy. Charge‐reversed cationic are engineered mRNA by anchoring targeting optimally arginine‐rich motifs into anionic exosome bilayer using buffer pH a charge‐reversal switch. Cationic penetrated through full‐thickness early‐stage arthritic human owing weak‐reversible ionic binding with GAGs efficiently delivered encapsulated eGFP residing tissue deep layers, while unmodified do not. When intra‐articularly injected destabilized medial meniscus mice knees OA, loaded charge‐reversed overcame joint clearance rapidly creating an intra‐tissue depot expressing eGFP; native remained unsuccessful. thus hold strong translational platform technology cartilage‐targeted any relevant targets OA treatment.

Language: Английский

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Extracellular vesicles as carriers of mRNA: Opportunities and challenges in diagnosis and treatment

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 2265 - 2289

Published: Jan. 1, 2024

Extracellular vesicles (EVs) are produced by all cells in the body. These biological nanoparticles facilitate cellular communication through transport of diverse cargoes, including small molecules, proteins, and nucleic acids. mRNA cargoes have gained particular interest given their role translation functional proteins. As a biomarker platform, EVs can be found nearly biofluids-blood, mucus, urine, cerebrospinal fluid, saliva-providing real-time insight into parent cell tissue function. mRNAs carried protected from degradation, resulting improved detection compared to free mRNA, recent work demonstrates promising results using these as biomarkers for cancer, neurological diseases, infectious gynecologic obstetric outcomes. Furthermore, innate cargo carrying, targeting, barrier crossing abilities EVs, structures been proposed therapeutic carriers mRNA. Recent advances demonstrate methods loading range disease indications. Here, we review studies diagnostics therapeutics. We discuss challenges associated with diagnostic applications highlight opportunities future development.

Language: Английский

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