From hope to healing: Exploring the therapeutic potential of exosomes in spinal cord injury DOI Creative Commons
Nidhi Singh, Lahanya Guha, Hemant Kumar

et al.

Extracellular Vesicle, Journal Year: 2024, Volume and Issue: 3, P. 100044 - 100044

Published: May 13, 2024

Spinal cord injury (SCI) is the damage to spinal causing paralysis below site compromised patient life quality. Exosomes are nanosized vesicles released during physiological or pathological processes. They present a promising avenue for therapeutic drug delivery due their tissue specificity and biocompatibility, offering enhanced efficacy with reduced accumulation-based toxicity. In SCI, exosomes target inflammation, apoptosis, microglial polarization, autophagy, contributing interventions. This article comprehensively explores pathophysiology of diverse exosome synthesis processes, limitations challenges overcome, potential from various cellular sources in SCI treatment.

Language: Английский

Neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke DOI Creative Commons
Lukui Chen, Zhihan Zhu, Jia Feng

et al.

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 18(2), P. 404 - 404

Published: July 18, 2022

Our previous study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes (hNSC-Exo) in ischemic stroke. Here, we loaded brain-derived neurotrophic factor (BDNF) into derived from NSCs to construct engineered (BDNF-hNSC-Exo) and compared their effects with those hNSC-Exo on stroke both vitro vivo. In a model H2O2-induced oxidative stress NSCs, BDNF-hNSC-Exo markedly enhanced cell survival. rat middle cerebral artery occlusion model, not only inhibited activation microglia, but also promoted differentiation endogenous neurons. These results suggest that BDNF can improve function NSC-derived treatment research may support clinical use other factors for central nervous system diseases.

Language: Английский

Citations

71

Exosome-mediated delivery and regulation in neurological disease progression DOI Creative Commons
Gurpreet Singh,

Ankit Mehra,

Sanchit Arora

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 264, P. 130728 - 130728

Published: March 11, 2024

Exosomes (EXOs), minute membranous structures originating from diverse biological sources, have recently seized the attention of researchers due to their theranostic potential for neurological diseases. Released actively by various cells, including stem adipose tissue, and immune EXOs wield substantial regulatory influence over intricate landscape complications, exhibiting both positive negative modulatory effects. In AD, play a pivotal role in disseminating breaking down amyloid-β protein. Moreover, derived mesenchymal cells showcase remarkable capacity mitigate pro-inflammatory phenotypes regulating miRNAs neurodegenerative These vesicles possess unique ability traverse blood-brain barrier, governing aggregation mutant huntingtin Understanding exosomal functions within CNS holds significant promise enhancing treatment efficacy This review intricately examines mechanisms involving disease development, highlighting therapeutic prospects exploring utility exosome-based nanomedicine complications. Additionally, delves into challenges associated with drug delivery brain, emphasizing complexities inherent this critical aspect neurotherapeutics.

Language: Английский

Citations

31

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy DOI Creative Commons
Tong Yu, Lili Yang, Ying Zhou

et al.

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

Published: Jan. 2, 2024

Abstract Spinal cord injury (SCI) is a catastrophic to the central nervous system (CNS) that can lead sensory and motor dysfunction, which seriously affects patients' quality of life imposes major economic burden on society. The pathological process SCI divided into primary secondary injury, cascade amplified responses triggered by injury. Due complexity mechanisms SCI, there no clear effective treatment strategy in clinical practice. Exosomes, are extracellular vesicles endoplasmic origin with diameter 30–150 nm, play critical role intercellular communication have become an ideal vehicle for drug delivery. A growing body evidence suggests exosomes great potential repairing SCI. In this review, we introduce exosome preparation, functions, administration routes. addition, summarize effect mechanism various repair review efficacy combination other strategies Finally, challenges prospects use described.

Language: Английский

Citations

16

Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury DOI Creative Commons

Yuluo Rong,

Zhuanghui Wang,

Pengyu Tang

et al.

Bioactive Materials, Journal Year: 2022, Volume and Issue: 23, P. 328 - 342

Published: Nov. 25, 2022

Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending on specific functionalized EVs appropriate engineering strategy. In this study, we demonstrated design drug delivery peptide CAQK-modified, siRNA-loaded (C-EVs-siRNA) SCI-targeted therapy. The CAQK was anchored through chemical modification membranes isolated from induced neural stem cells (iNSCs). CCL2-siRNA then loaded into electroporation. modified still maintained basic properties showed favorable targeting effects in vitro vivo. C-EVs-siRNA specifically delivered siRNA region taken up by target cells. used inherent anti-inflammatory neuroreparative functions iNSCs-derived synergy with siRNA, thus enhancing effect against SCI. combination targeted effectively regulated microenvironmental disturbance after SCI, promoted transformation microglia/macrophages M1 M2 limited negative inflammatory response neuronal functional recovery mice Thus, engineered potentially feasible efficacious treatment may also be develop other diseases.

Language: Английский

Citations

58

The PI3K/AKT Pathway—The Potential Key Mechanisms of Traditional Chinese Medicine for Stroke DOI Creative Commons
Chenyang Gu, Qiankun Zhang, Yajing Li

et al.

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: May 31, 2022

Stroke is associated with a high disability and fatality rate, adversely affects the quality of life patients their families. Traditional Chinese Medicine (TCM) has been used effectively in treatment stroke for more than 2000 years China surrounding countries regions, over years, this field gleaned extensive clinical experience. The Phosphatidylinositol 3 kinase (PI3K)/protein B (AKT) pathway important regulation cell migration, proliferation, differentiation, apoptosis, plays vital role vascularization oxidative stress stroke. Current Western medicine protocols include mainly pharmacologic or mechanical thrombectomy to restore blood flow. This review collates recent advances past 5 TCM involving PI3K/AKT pathway. significantly reduces neuronal damage, inhibits delays progression via various PI3K/AKT-mediated downstream pathways. In future, can provide new perspectives directions exploring key factors, effective activators inhibitors that affect occurrence stroke, thereby facilitating treatment.

Language: Английский

Citations

44

Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway DOI Creative Commons
Chengjun Li, Tian Qin, Yudong Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 20, 2022

Spinal cord injury (SCI) is a catastrophic event mainly involving neuronal apoptosis and axonal disruption, it causes severe motor sensory deficits. Due to the complicated pathological process of SCI, there currently still lack effective treatment for SCI. Microglia, type immune cell residing in central nervous system (CNS), need respond various stimuli protect cells from death. It was also reported that microRNAs (miRNAs) had been identified microglia-derived exosomes can be taken up by neurons. However, kinds miRNAs exosome cargo derived microglia underlying mechanisms which they contribute neuroprotection after SCI remain unknown. In present study, contusive mouse model vitro experiments were applied explore therapeutic effects on apoptosis, regrowth, functional recovery Then, miRNA analysis, rescue experiments, luciferase activity assays target genes performed confirm role mechanism exosomal We revealed could promote neurological suppressing promoting regrowth both vivo vitro. MicroRNA-151-3p abundant necessary mediating neuroprotective effect repair. Luciferase P53 gene miR-151-3p p53/p21/CDK1 signaling cascades may involved modulation microRNA-151-3p. conclusion, our data demonstrated (microglia-Exos) might promising, cell-free approach key molecule mediates treatments.

Language: Английский

Citations

41

Targeted Delivery of RGD-CD146+CD271+ Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promotes Blood–Spinal Cord Barrier Repair after Spinal Cord Injury DOI
Yong Xie, Yi Sun, Yudong Liu

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(18), P. 18008 - 18024

Published: Sept. 11, 2023

Spinal cord injury (SCI) disrupts the blood-spinal barrier (BSCB), potentially exacerbating nerve damage and emphasizing criticality of preserving BSCB integrity during SCI treatment. This study explores an alternative therapeutic approach for by identifying a subpopulation exosomes with stable function achieving specific targeted delivery. Specific subpopulations CD146+CD271+ umbilical mesenchymal stem cells (UCMSCs) were isolated, from which engineered (RGD-CD146+CD271+ UCMSC-Exos) neovascularization obtained through gene transfection. In vivo in vitro experiments performed to explore targeting effects RGD-CD146+CD271+ UCMSC-Exos potential mechanisms underlying stabilization neural recovery. The results demonstrated that exhibited physical chemical properties similar those regular exosomes. Notably, following intranasal administration, enhanced aggregation at center neovascular endothelial cells. model, administration reduced Evans blue dye leakage, increased tight junction protein expression, improved neurological testing revealed treatment significantly permeability bEnd.3 subjected oxygen-glucose deprivation, thereby restoring junctions. Moreover, further exploration molecular mechanism identified crucial role miR-501-5p/MLCK axis this process. conclusion, delivery presents promising effective option SCI.

Language: Английский

Citations

33

The Exosome-Mediated PI3K/Akt/mTOR Signaling Pathway in Neurological Diseases DOI Creative Commons
Amin Iranpanah, Leila Kooshki, Seyed Zachariah Moradi

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 1006 - 1006

Published: March 21, 2023

As major public health concerns associated with a rapidly growing aging population, neurodegenerative diseases (NDDs) and neurological are important causes of disability mortality. Neurological affect millions people worldwide. Recent studies have indicated that apoptosis, inflammation, oxidative stress the main players NDDs critical roles in processes. During aforementioned inflammatory/apoptotic/oxidative procedures, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target rapamycin (mTOR) pathway plays crucial role. Considering functional structural aspects blood–brain barrier, drug delivery to central nervous system is relatively challenging. Exosomes nanoscale membrane-bound carriers can be secreted by cells carry several cargoes, including proteins, nucleic acids, lipids, metabolites. significantly take part intercellular communications due their specific features low immunogenicity, flexibility, great tissue/cell penetration capabilities. Due ability cross these nano-sized structures been introduced as proper vehicles for multiple studies. In present systematic review, we highlight potential therapeutic effects exosomes context targeting PI3K/Akt/mTOR signaling pathway.

Language: Английский

Citations

28

Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury DOI Open Access
Zin Z. Khaing, Jessica Y. Chen, Gevick Safarians

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3824 - 3824

Published: Feb. 14, 2023

Spinal cord injury (SCI) often causes loss of sensory and motor function resulting in a significant reduction quality life for patients. Currently, no therapies are available that can repair spinal tissue. After the primary SCI, an acute inflammatory response induces further tissue damage process known as secondary injury. Targeting to prevent additional during subacute phases SCI represents promising strategy improve patient outcomes. Here, we review clinical trials neuroprotective therapeutics expected mitigate injury, focusing primarily on those last decade. The strategies discussed broadly categorized acute-phase procedural/surgical interventions, systemically delivered pharmacological agents, cell-based therapies. In addition, summarize potential combinatorial considerations.

Language: Английский

Citations

26

Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats DOI

Hosna Cheshmi,

Hossein Mohammadi,

Mitra Akbari

et al.

Neurotoxicity Research, Journal Year: 2023, Volume and Issue: 41(5), P. 431 - 445

Published: May 8, 2023

Language: Английский

Citations

26