Mesenchymal Stem Cells Prevent SLC39A14‐Dependent Hepatocyte Ferroptosis through Exosomal miR‐16‐5p in Liver Graft DOI Creative Commons

Zhizhao Deng,

Weiqi Zeng,

Yingxin Gao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Ischemia‐reperfusion injury (IRI) is the leading cause of hepatic graft dysfunction, resulting from hepatocyte damage. Nevertheless, given few specialized therapeutics available in IRI, additional mechanistic insights into damage are required. Here, protein solute carrier family 39 member 14 (SLC39A14) identified as a pro‐ferroptosis target hepatocytes human liver allografts through single‐cell RNA sequencing analysis. SLC39A14 knockdown significantly mitigated IRI by preventing ferroptosis vivo and vitro. Mechanistically, inhibition suppressed non‐transferrin‐bound iron (NTBI) uptake hepatocytes, thereby reducing overload cell ferroptosis. Moreover, bone marrow‐derived mesenchymal stem cells (hBMSCs) found to exhibit notable therapeutic effect on downregulating expression. Exosomes derived hBMSCs delivered abundant miR‐16‐5p which post‐transcriptionally expression reduced induced IRI. In conclusion, triggers mediating NTBI inducing hBMSC‐based therapy promising reverse this progression

Language: Английский

Fully Bioactive Nanodrugs: Stem Cell-Derived Exosomes Engineered with Biomacromolecules to Treat CCl4- and Extreme Hepatectomy-Induced Acute Liver Failure DOI
Meng Sun, Min Li, Min Hu

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(50), P. 33907 - 33921

Published: Dec. 3, 2024

Acute liver failure (ALF) is a serious global disease characterized by rapid onset and high mortality. Currently, the clinical treatment of ALF faces considerable hurdles due to limited medication options scarcity transplants. Despite biomacromolecules such as hepatocyte growth factor (HGF) glutathione (GSH) having been applied for symptom relief in clinic, they still face substantial challenges including poor stability, difficulty acting on intracellular targets, inadequate therapeutic outcome. In this work, taking advantage innate targeting regenerative capabilities mesenchymal stem cells (MSCs), we harnessed MSC-derived exosomes natural bioactive carriers simultaneous delivery HGF GSH, forming fully nanodrug termed HG@Exo. Impressively, HG@Exo demonstrated potent effects against both carbon tetrachloride (CCl

Language: Английский

Citations

2

Artificial Nanovesicles Derived from Cells: A Promising Alternative to Extracellular Vesicles DOI

Saiyun Lou,

Wei Hu,

Pengyao Wei

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

As naturally secreted vesicles by cells, extracellular (EVs) play essential roles in modulating cell–cell communication and have significant potential tissue regeneration, immune regulation, drug delivery. However, the low yield uncontrollable heterogeneity of EVs been obstacles to their widespread translation into clinical practice. Recently, it has discovered that artificial nanovesicles (NVs) produced cell processing can inherit components functions parent cells possess similar structures EVs, with significantly higher yields more flexible functionalization, making them a powerful complement natural EVs. This review focuses on recent advances research NVs as replacements for We provide an overview comparing summarize top-down preparation strategies NVs. The applications prepared from stem differentiated engineered are presented, well latest NV engineering. Finally, main challenges discussed.

Language: Английский

Citations

2

Concurrent immune checkpoint blockade for enhanced cancer immunotherapy utilizing engineered hybrid nanovesicles DOI Creative Commons
Yuxuan Liu,

Fuxu Yang,

Zhimin Li

et al.

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

Published: Nov. 11, 2024

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, demonstrating unprecedented efficacy against advanced cancers. However, their clinical applications are significantly hampered by low overall response rates. Dual blockade of two immune checkpoints represents a promising strategy to enhance immunotherapeutic efficacy. In this study, we developed hybrid cell membrane nanovesicles adorned with PD-1 and SIRPα receptors for combination immunotherapy in melanoma. Our (PD-1/SIRPα NVs) demonstrated high specificity PD-L1 CD47 ligands, facilitating the phagocytosis melanoma cells macrophages. mouse model, PD-1/SIRPα NVs suppressed 77% tumor growth elicited robust antitumor immunotherapy. conclusion, our findings highlight potential as novel effective ICIs

Language: Английский

Citations

1

Engineering Strategies of Plant-Derived Exosome-Like Nanovesicles: Current Knowledge and Future Perspectives DOI Creative Commons
Yuhan Li, Yulong Wang,

Hongrui Zhao

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 12793 - 12815

Published: Nov. 1, 2024

Plant-derived exosome-like nanovesicles (PELNs) from edible plants, isolated by ultracentrifugation, size exclusion chromatography or other methods, were proved to contain a variety of biologically active and therapeutically specific components. Recently, investigations in the field PELN-based biomedicine have been conducted, which positioned those as promising tools for prevention treatment several diseases, with their natural origin potentially offering superior biocompatibility bioavailability. However, inadequate targeting limited therapeutic effects constrain utility clinical translation PELNs. Thus, strategies aiming at bridging gap engineering PELNs great interest. Those approaches include membrane hybridization, physical chemical surface functionalization encapsulation payloads. Herein, we provide comprehensive overview biogenesis composition, isolation purification methods characterization PELNs, well functions. Current knowledge on construction biomedical application engineered reviewed. Additionally, future directions perspectives this discussed order further enrich expand prospects

Language: Английский

Citations

1

Mesenchymal Stem Cells Prevent SLC39A14‐Dependent Hepatocyte Ferroptosis through Exosomal miR‐16‐5p in Liver Graft DOI Creative Commons

Zhizhao Deng,

Weiqi Zeng,

Yingxin Gao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Ischemia‐reperfusion injury (IRI) is the leading cause of hepatic graft dysfunction, resulting from hepatocyte damage. Nevertheless, given few specialized therapeutics available in IRI, additional mechanistic insights into damage are required. Here, protein solute carrier family 39 member 14 (SLC39A14) identified as a pro‐ferroptosis target hepatocytes human liver allografts through single‐cell RNA sequencing analysis. SLC39A14 knockdown significantly mitigated IRI by preventing ferroptosis vivo and vitro. Mechanistically, inhibition suppressed non‐transferrin‐bound iron (NTBI) uptake hepatocytes, thereby reducing overload cell ferroptosis. Moreover, bone marrow‐derived mesenchymal stem cells (hBMSCs) found to exhibit notable therapeutic effect on downregulating expression. Exosomes derived hBMSCs delivered abundant miR‐16‐5p which post‐transcriptionally expression reduced induced IRI. In conclusion, triggers mediating NTBI inducing hBMSC‐based therapy promising reverse this progression

Language: Английский

Citations

1