Research on the TSPAN6 regulating the secretion of ADSCs-Exos through syntenin-1 and promoting wound healing DOI Creative Commons

Zhihua Qiao,

Xiancheng Wang, Hongli Zhao

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 15, 2024

Exosomes (Exos) from adipose-derived stem cells (ADSCs) have a high inclusion content and low immunogenicity, which helps to control inflammation accelerate the healing of wounds. Unfortunately, yield exosomes is poor, raises expense lengthens treatment period in addition impairing exosomes' therapeutic impact. Thus, one key problems that needs be resolved current exosome study increasing yield. Tetraspanin-6 (TSPAN6) overexpression knockdown models ADSCs were constructed determine number secreted by each group as well multivesicular bodies (MVBs) intraluminal vesicles (ILVs) within cells. Subsequently, binding region interaction between TSPAN6 syntenin-1 was identified using yeast two-hybrid assay, itself immunoprecipitation. Finally, cellular animal studies conducted investigate role class exosomes. When compared group, intracellular MVBs ILVs significantly larger, ADSCsTSPAN6+-Exos more than three times higher. However, TSPAN6's ability stimulate secretion reduced result knockdown. Additional assay demonstrated critical structures for their N-terminal, Postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ1), PDZ2 domains syntenin-1, C-terminal TSPAN6. In trials, wound rate best while experiments better enhanced proliferation migration human skin fibroblasts (HSFs) umbilical vein endothelial (HUVECs). stimulates formation, creation ADSCs. Syntenin-1 essential stimulation ADSCs-Exos secretion. Furthermore, has greater support healing, angiogenesis, variety

Language: Английский

Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles DOI Creative Commons
Paola A. Castagnino, Derick A. Haas, Luca Musante

et al.

Cancer Biology & Therapy, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 26, 2025

Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was first defined and validated adaptive mechanism. The endoplasmic reticulum (ER) is central as modulatory secreted integral membrane proteins are dependent on ER. Sigma1 a unique ligand-regulated scaffolding protein enriched ER cells. PD-L1 an glycoprotein that translated into processed through cellular secretory pathway. At cell surface, checkpoint molecule binds PD-1 activated T-cells blocks immunity. can also be incorporated cell-derived extracellular vesicles (EVs), EV-associated inactivate within tumor microenvironment. Here, we demonstrate selective small inhibitor block mediated part altering incorporation EVs. inhibition blocked post-translational maturation downstream IFN-γ/STAT1 signaling. Subsequently, EVs released response stimulation were significantly less potent suppressors T-cell activation. These results suggest reducing derived suppressive EVs, may promote antitumor modulation presents novel approach regulating microenvironment content production Altogether, these data support notion play role

Language: Английский

Citations

2
Leveraging nature’s nanocarriers: Translating insights from extracellular vesicles to biomimetic synthetic vesicles for biomedical applications DOI Creative Commons
Yunxi Chen,

Noélie Douanne,

T.-C. Wu

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(9)

Published: Feb. 26, 2025

Naturally occurring extracellular vesicles (EVs) and synthetic nanoparticles like liposomes have revolutionized precision diagnostics medicine. EVs excel in biocompatibility cell targeting, while offer enhanced drug loading capacity scalability. The clinical translation of is hindered by challenges including low yield heterogeneity, whereas face rapid immune clearance limited targeting efficiency. To bridge these gaps, biomimetic (SVs) emerged as innovative platforms, combining the advantageous properties liposomes. This review emphasizes critical aspects EV biology, such mechanisms EV-cell interaction source-dependent functionalities modulation, tissue regeneration, informing SV engineering. We reviewed a broad array SVs, with focus on lipid bilayered functionalized proteins. These include cell-derived nanovesicles, protein-functionalized liposomes, hybrid vesicles. By addressing current highlighting opportunities, this aims to advance SVs for transformative biomedical applications.

Language: Английский

Citations

2
Dynamically controllable hot spots in DNA-derived hydrogel scaffold SERS substrate for exosome recognition using DNA self-assembly amplification DOI
Yeru Wang, Rongke Gao, Chao Ma

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 496, P. 154270 - 154270

Published: July 24, 2024

Language: Английский

Citations

6
Composition, functions, and applications of exosomal membrane proteins DOI Creative Commons
Fang Xu,

Shumin Luo,

Peng‐Peng Lü

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 1, 2024

Exosomes play a crucial role in various biological processes, such as human development, immune responses, and disease occurrence. The membrane proteins on exosomes are pivotal factors for their functionality. Currently, numerous have been identified exosome membranes, participating intercellular communication, mediating target cell recognition, regulating processes. Furthermore, from derived cancer cells can serve relevant biomarkers early diagnosis. This article provides comprehensive review of the composition diverse functions organism's Through in-depth exploration proteins, it is expected to offer essential foundations future development novel biomedical diagnostics therapies.

Language: Английский

Citations

5
Mesenchymal stromal cell exosomes for drug delivery of prostate cancer treatments: a review DOI Creative Commons

Chengran Wang,

Yanling Feng,

Xianfang Rong

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 23, 2025

Interest in prostate cancer as a research topic has gradually increased. As result, series of innovative treatment strategies have emerged with an in-depth understanding the disease. Owing to their unique biological characteristics, mesenchymal stromal cell exosomes (MSC-Exos) garnered significant attention for potential deliver targeted drugs and enable precise treatment. Herein, MSC-Exos drug-delivery systems is reviewed. This review provides comprehensive introduction advantages these systems, current trends progress, well analysis challenges future directions. Moreover, this lays solid foundation continued development application MSC-Exos.

Language: Английский

Citations

0
Tetraspanin CD9 alters cellular trafficking and endocytosis of tetraspanin CD63, affecting CD63 packaging into small extracellular vesicles DOI Creative Commons
Leanne C. Duke, Allaura S. Cone, Li Sun

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108255 - 108255

Published: Feb. 1, 2025

Small extracellular vesicles (sEVs) are particles secreted from cells that play vital roles both in normal physiology and human disease. sEVs highly enriched tetraspanin proteins, such as CD9 CD63, contain tetraspanin-enriched membrane microdomains involved loading of with macromolecule cargoes sEV biogenesis. However, the precise individual tetraspanins biogenesis cargo remain poorly understood. Here, we report negatively regulated CD63 trafficking to its subsequent packaging into small EVs, whereas had no discernable effect on localization or packaging. Using super resolution microscopy vesicles, showed governs fraction loaded CD63. Interestingly, CD9-dependent suppression was rescued by pharmacological blockade endocytosis. Together, our data support a model where contributes regulation secretion an endocytosis-dependent manner reprogram contents microdomains.

Language: Английский

Citations

0
Inter-Tissue Communication Mechanisms via Exosomes and Their Implications in Metabolic Diseases: Opportunities for Pharmacological Regulation DOI Creative Commons
Brenda Chimal-Vega,

Jesus Emanuel Maldonado-Arvizu,

Alicia Ávalos

et al.

Future Pharmacology, Journal Year: 2025, Volume and Issue: 5(1), P. 11 - 11

Published: March 6, 2025

Exosomes can transport regulatory biomolecules and are mediators of cellular signaling among metabolic tissues through endocrine mechanisms. Understanding the pathways processes underlying exosome-mediated inter-tissue communication is critical for elucidating molecular pathophysiology diseases such as obesity, type 2 diabetes mellitus (T2DM), cardiovascular disorders. Consequently, these mechanisms represent novel promising targets pharmacological regulation. We examined current knowledge regarding exosome physiology, interaction with target tissues, its role in tissue communication. also analyzed secretory profiles exosomes emphasizing their roles adipose tissue, liver, pancreas, skeletal muscle, small intestine, while discussing association diseases. In this sense, we propose exosomal pentad a framework highlighting inter-organ communication, where may regulate axis involving tissues. This model aligns ominous octet but emphasizes key regulators homeostasis potential therapeutic targets. The treatment emerges area pharmacologic exploration. For instance, strategies that prevent binding or expression cargo molecules miRNAs could be designed, using antagomiRs nanoparticles. Additionally, integrins like αvβ5 on membrane blocked monoclonal antibodies engineered targeted delivery molecules. Exosomes, regulation, hold to design precise molecular-level therapies minimizing systemic side effects.

Language: Английский

Citations

0
Genetic tools for investigating the life cycle of extracellular vesicles DOI
Wenyi Zheng, Samantha Roudi,

Houze Zhou

et al.

Nature Reviews Bioengineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

0
Tumor cell-derived engineered exosome enhances effective immunotherapy for orthotopic glioblastoma and its recurrences DOI Creative Commons
Shanshan Li,

Dongya Zhang,

Yibin Wang

et al.

Nano Today, Journal Year: 2025, Volume and Issue: 63, P. 102748 - 102748

Published: April 8, 2025

Language: Английский

Citations

0
Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers DOI Creative Commons
Brianna Hnath, Nikolay V. Dokholyan

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease resulting in paralysis and death within three to five years. Mutations over forty different proteins have been linked ALS, leading controversy whether ALS one or many diseases with similar phenotype. Cu,Zn superoxide dismutase 1 (SOD1) are only found 2-3% of cases, yet misfolded SOD1 both sporadic (sALS) familial (fALS) patients. Yet, mutations TDP-43 FUS increase the level on extracellular vesicles (EVs). Additionally, small EVs isolated from patient samples caused cell wild type motor neurons myotubules. The toxicity protein alterations led theory that responsible for spread ALS. We hypothesize previously-identified toxic trimeric spreading altering other ALS-related proteins, linking them common mechanism. To test our hypothesis, we isolate neuron-like cells expressing trimer stabilizing perform sandwich enzyme-linked immunoassay (ELISA) (CD9 capture antibody) quantify 17 decrease stabilization. identify which EV release pathway being affected by utilizing endocytosis exocytosis inhibitors, determine if any specific EV-related altered establish VAPB, VCP, Stathmin-2 between ALS-associated multiple pathways, including Caveolae pathway, suggesting novel hybrid present

Language: Английский

Citations

0