Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells

Li, Rongrong; Wang, Chen; Zhou, Manqian; Liu, Yue; Chen, Shang; Chai, Zihan; Hu, Huang; Zhang, Kaiyue; Han, Zhibo; Hua, Guoqiang; Benkirane‐Jessel, Nadia; Han, Zhongchao; Li, Zongjin

doi:10.1016/j.vesic.2022.100018

Cited by 9 publications

(3 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We provide direct evidence that LSC-Exo expresses enriched hACE2 and can cross the air-blood-barrier to reach and accumulate in trachea, bronchioles, and deep lung parenchyma after nebulization. Importantly, LSC-Exo significantly prevents SARS-CoV-2 infection in Syrian hamsters, a model of severe COVID-19 disease 35 , by a drastically reduced viral load, diminished lung inflammation, and dampened viral pneumonia. More importantly, we demonstrate that LSC-Exo preserves the neutralizing capacity against D614G and B.1.617.2 (Delta) pseudoviruses.…”

Section: Introductionmentioning

confidence: 98%

Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2

Wang,

Hu,

Popowski

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.

show abstract

Section: Introductionmentioning

confidence: 98%

Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2

Wang,

Hu,

Popowski

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Extracellular vesicles (EVs) are heterogeneous phospholipid membrane-bound vesicles that are released by various cells [1,2]. Extracellular vesicles can be classified as exosomes, microvesicles, and apoptotic bodies, based on their size and biogenesis processes [1,3].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles: A new frontier in the theranostics of cardiovascular diseases

Fu,

2024

iRADIOLOGY

Self Cite

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are tiny vesicles released by various cells that contain a variety of proteins, lipids, and nucleic acids, which can have a wide range of effects on other cells. The dynamic composition and contents of EVs can serve as sensitive biomarkers for diagnosing and monitoring various cardiovascular diseases (CVDs). In addition to their diagnostic potential, EVs are therapeutic agents capable of precise modulation and amelioration of CVDs, because of their innate ability to encapsulate and deliver bioactive molecules. This growing field reveals the intricate interplay between EVs and cardiovascular pathophysiology, showing that EVs can act as messengers of intercellular communication for CVD regenerative therapy. Extracellular vesicles serve as dual agents in the field of theranostics, both as diagnostic biomarkers able to decode nuanced molecular signatures of CVDs and as potent vehicles for targeted therapeutic interventions. This review delves into the evolving landscape of EVs, uncovering their diagnostic and therapeutic prospects and emphasizing their growing importance in shaping the future of cardiovascular theranostics.

show abstract

“…Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can differentiate into numerous cell types and are present in several tissues [ 5 – 7 ]. Increasing evidence of MSC migration to lung injury and their contribution to lung regeneration attracts attention for the treatment of ALI/ARDS [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation

Hezam

Wang

et al. 2023

Stem Cell Res Ther

Self Cite

View full text Add to dashboard Cite

Background Mesenchymal stem cells (MSCs) have demonstrated remarkable therapeutic promise for acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS). MSC secretomes contain various immunoregulatory mediators that modulate both innate and adaptive immune responses. Priming MSCs has been widely considered to boost their therapeutic efficacy for a variety of diseases. Prostaglandin E2 (PGE2) plays a vital role in physiological processes that mediate the regeneration of injured organs. Methods This work utilized PGE2 to prime MSCs and investigated their therapeutic potential in ALI models. MSCs were obtained from human placental tissue. MSCs were transduced with firefly luciferase (Fluc)/eGFP fusion protein for real-time monitoring of MSC migration. Comprehensive genomic analyses explored the therapeutic effects and molecular mechanisms of PGE2-primed MSCs in LPS-induced ALI models. Results Our results demonstrated that PGE2-MSCs effectively ameliorated lung injury and decreased total cell numbers, neutrophils, macrophages, and protein levels in bronchoalveolar lavage fluid (BALF). Meanwhile, treating ALI mice with PGE2-MSCs dramatically reduced histopathological changes and proinflammatory cytokines while increasing anti-inflammatory cytokines. Furthermore, our findings supported that PGE2 priming improved the therapeutic efficacy of MSCs through M2 macrophage polarization. Conclusion PGE2-MSC therapy significantly reduced the severity of LPS-induced ALI in mice by modulating macrophage polarization and cytokine production. This strategy boosts the therapeutic efficacy of MSCs in cell-based ALI therapy.

show abstract

Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells

Cited by 9 publications

References 42 publications

Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2

Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2

Extracellular vesicles: A new frontier in the theranostics of cardiovascular diseases

Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation

Contact Info

Product

Resources

About