Engineering extracellular vesicles by three‐dimensional dynamic culture of human mesenchymal stem cells

Journal of Extracellular Vesicles, Journal Year: 2022, Volume and Issue: 11(6)

Published: June 1, 2022

Human mesenchymal stem cell (hMSC) derived extracellular vesicles (EVs) have shown therapeutic potential in recent studies. However, the corresponding components are largely unknown, and scale-up production of hMSC EVs is a major challenge for translational applications. In current study, hMSCs were grown as 3D aggregates under wave motion to promote EV secretion. Results demonstrate that activation endosomal sorting complexes required transport (ESCRT)-dependent -independent pathways. mRNA sequencing revealed global transcriptome alterations aggregates. Compared 2D-hMSC-EVs, quantity 3D-hMSC-EVs was enhanced significantly (by 2-fold), with smaller sizes, higher miR-21 miR-22 expression, an altered protein cargo (e.g., upregulation cytokines anti-inflammatory factors) uncovered by proteomics analysis, possibly due biogenesis. Functionally, rejuvenated senescent cells exhibited immunomodulatory potentials. summary, this study provides promising strategy scalable high-quality from potential.

Language: Английский

---

Extracellular vesicles as bioactive nanotherapeutics: An emerging paradigm for regenerative medicine

Theranostics, Journal Year: 2022, Volume and Issue: 12(11), P. 4879 - 4903

Published: Jan. 1, 2022

In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis tissue repair, have emerged one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review latest progress EVs applications. Firstly, will briefly introduce biogenesis, function isolation technology EVs. Then, underlying therapeutic mechanisms native unmodified engineering strategies modified entities be discussed. Subsequently, main focus placed on repair regeneration applications organs brain, heart, bone cartilage, liver kidney, well skin. More importantly, current clinical trials medicine also highlighted. Finally, future challenges insightful perspectives currently developed EV-based biomedicine short, opened new horizons biologists, chemists, nanoscientists, pharmacists, clinicians, making possible powerful tools therapies

Language: Английский

---

Preconditioning and Engineering Strategies for Improving the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cell-Free Therapy

Stem Cells International, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 18

Published: May 14, 2022

Mesenchymal stem cells (MSCs) have been widely applied to regenerative medicine owing their multiple differentiation, self-renewal, and immunomodulatory abilities. Exosomes are cell-secreted natural nanovesicles thought be mediators of intercellular communication material transport. The therapeutic potential MSCs can largely attributed MSC-derived exosomes (MSC-exosomes). Emerging evidence suggests that the efficacy MSC-exosomes is highly dependent on status MSCs, optimization extracellular environment affects exosomal content. Pretreatment methods including three-dimensional cultures, hypoxia, other biochemical cues shown potentially enhance biological activity while maintaining or enhancing production. On hand, engineering means desired function has rapidly gaining attention. In particular, biologically active molecule encapsulation membrane modification alter functions targeting MSC-exosomes. this review, we summarize two possible strategies improve MSC-exosomes: preconditioning approaches exosomes. We also explore underlying mechanisms different discuss advantages limitations upcoming clinical applications.

Language: Английский

---

New strategies of neurodegenerative disease treatment with extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs)

Theranostics, Journal Year: 2023, Volume and Issue: 13(12), P. 4138 - 4165

Published: Jan. 1, 2023

Neurodegenerative diseases are characterized by the progressive loss of neurons and intricate interactions between different cell types within affected regions.Reliable biomarkers that can accurately reflect disease activity, diagnose, monitor progression neurodegenerative crucial for development effective therapies.However, identifying suitable has been challenging due to heterogeneous nature these diseases, affecting specific subsets in brain regions.One promising approach promoting regeneration recovery involves transplantation mesenchymal stem cells (MSCs).MSCs have demonstrated ability modulate immune system, promote neurite outgrowth, stimulate angiogenesis, repair damaged tissues, partially through release their extracellular vesicles (EVs).MSC-derived EVs retain some therapeutic characteristics parent MSCs, including regulate facilitate tissue repair.This review aims explore potential MSC-derived as an emerging strategy highlighting role modulating neuronal recovery.By elucidating mechanisms which exert effects, we advance our understanding leverage novel treatment approaches field diseases.

Language: Английский

---

Recent advances in biomimetic nanodelivery systems: New brain-targeting strategies

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 358, P. 439 - 464

Published: May 13, 2023

Language: Английский

---

Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access

Bioactive Materials, Journal Year: 2023, Volume and Issue: 29, P. 16 - 35

Published: June 28, 2023

Neurodegenerative diseases represent a growing burden on healthcare systems worldwide. Mesenchymal stem cells (MSCs) have shown promise as potential therapy due to their neuroregenerative, neuroprotective, and immunomodulatory properties, which are, however, linked the bioactive substances they release, collectively known secretome. This paper provides an overview of most recent research safety efficacy MSC-derived secretome extracellular vesicles (EVs) in clinical (if available) preclinical models Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis, multiple Huntington's acute ischemic stroke, spinal cord injury. The article explores biologically active within MSC-secretome/EVs, mechanisms responsible for observed therapeutic effects, strategies that may be used optimize MSC-secretome/EVs production based specific needs. review concludes with critical discussion current trials perspective future directions translating MSC-secretome EVs into clinic, specifically regarding how address challenges associated pharmaceutical manufacturing, including scalability, batch-to-batch consistency, adherence Good Manufacturing Practices (GMP) guidelines, formulation, storage, along quality controls, access market relative costs, value money impact total expenditure.

Language: Английский

---

Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease

Theranostics, Journal Year: 2023, Volume and Issue: 13(4), P. 1264 - 1285

Published: Jan. 1, 2023

With the increase of population aging, number Alzheimer's disease (AD) patients is also increasing.According to current estimates, approximately 11% people over 65 suffer from AD, and that percentage rises 42% among 85.However, no effective treatment capable decelerating or stopping AD progression available.Furthermore, AD-targeted drugs composed synthetic molecules pose concerns regarding biodegradation, clearance, immune response, neurotoxicity.Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are essential intercellular communication mediators holding great promise as therapeutics owing their biocompatibility, versatility, effortless storage, superior safety, ability transport messenger noncoding RNAs, proteins, lipids, DNAs, other bioactive compounds derived cells.The functionalisation engineering strategies MSC-EVs highlighted (e.g.preconditioning, drug loading, surface modification, artificial EV fabrication), which could improve by multiple therapeutic effects, including clearing abnormal protein accumulation achieving neuroprotection immunomodulatory effects.Herein, this review summarises state-of-the-art engineer MSC-EVs, discusses progress in use therapeutics, presents perspectives challenges associated with related clinical applications, concludes engineered show immense potential therapy.

Language: Английский

---

Cell–cell communication: new insights and clinical implications

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

Published: Aug. 7, 2024

Multicellular organisms are composed of diverse cell types that must coordinate their behaviors through communication. Cell-cell communication (CCC) is essential for growth, development, differentiation, tissue and organ formation, maintenance, physiological regulation. Cells communicate direct contact or at a distance using ligand-receptor interactions. So cellular encompasses two processes: signal conduction generation intercellular transmission signals, transduction reception procession signals. Deciphering networks critical understanding metabolism. First, we comprehensively review the historical milestones in CCC studies, followed by detailed description mechanisms molecule importance main signaling pathways they mediate maintaining biological functions. Then systematically introduce series human diseases caused abnormalities progress clinical applications. Finally, summarize various methods monitoring interactions, including imaging, proximity-based chemical labeling, mechanical force analysis, downstream analysis strategies, single-cell technologies. These aim to illustrate how functions depend on these interactions complexity regulatory regulate crucial processes, homeostasis, immune responses diseases. In addition, this enhances our processes occur after cell-cell binding, highlighting its application discovering new therapeutic targets biomarkers related precision medicine. This collective provides foundation developing targeted drugs personalized treatments.

Language: Английский

---

Exosome-mediated delivery and regulation in neurological disease progression

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

---

The role of exosomes in diagnosis, pathophysiology, and management of Alzheimer's Disease

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 754, P. 151526 - 151526

Published: Feb. 22, 2025

Language: Английский

---