Extracellular vesicles from neural progenitor cells promote functional recovery after stroke in mice with pharmacological inhibition of neurogenesis DOI Creative Commons
Aura N. Campero-Romero, Fernando H. Real, Ricardo A. Santana-Martínez

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 28, 2023

Neural progenitor cells (NPCs) of the subventricular zone proliferate in response to ischemic stroke adult mouse brain. Newly generated have been considered influence recovery following a stroke. However, mechanism underlying such protection is matter active study since it has thought that proliferating NPCs mediate their protective effects by secreting soluble factors promote rather than neuronal replacement penumbra. We tested hypothesis this mediated secretion multimolecular complexes extracellular vesicles (EVs). found molecular oxygen and glucose-deprived (OGD) NPCs-derived EVs very limited improving overt neurological alterations caused compared our recently reported astrocyte-derived EVs. when we inhibited ischemia-triggered proliferation with chronic administration DNA synthesis inhibitor Ara-C, effect NPC-derived became evident, suggesting endogenous exerted NPC mainly carried out through involves intercellular communication analyzed proteomic content cargo label-free relative abundance mass spectrometry identified several mediators within these vesicles. Our findings indicate are against cascade activated and, thus, hold significant therapeutic potential.

Language: Английский

A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine DOI Creative Commons

Soudeh Moghadasi,

Marischa Elveny, Heshu Sulaiman Rahman

et al.

Journal of Translational Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: July 12, 2021

Abstract Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs not related differentiation potentials, but rather exerted through release soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, owning targeting capability organotropism, exosomes considered nanocarriers possible use in diagnosis therapy. Exosomes convey functional molecules such long non-coding RNAs (lncRNAs) micro-RNAs (miRNAs), proteins (e.g., chemokine cytokine), lipids from target cells. They participate intercellular interaction procedures enable repair damaged or diseased tissues organs. Findings evidenced alone liable beneficial influences myriad experimental models, suggesting MSC- can be utilized establish novel cell-free therapeutic treatment varied human disorders, encompassing myocardial infarction (MI), CNS-related musculoskeletal disorders (e.g. arthritis), kidney diseases, liver lung well cutaneous wounds. Importantly, compared MSCs, serve more steady entities reduced safety risks concerning injection live cells, microvasculature occlusion risk. In current review, we will discuss potential an innovative approach context medicine highlight recent knowledge on translational medicine, focusing vivo researches.

Language: Английский

Citations

178
Neuroprotective Strategies for Ischemic Stroke—Future Perspectives DOI Open Access
Matteo Haupt, Stefan T. Gerner, Mathias Bähr

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4334 - 4334

Published: Feb. 22, 2023

Ischemic stroke is the main cause of death and most common acquired physical disability worldwide. Recent demographic changes increase relevance its sequelae. The acute treatment for restricted to causative recanalization restoration cerebral blood flow, including both intravenous thrombolysis mechanical thrombectomy. Still, only a limited number patients are eligible these time-sensitive treatments. Hence, new neuroprotective approaches urgently needed. Neuroprotection thus defined as an intervention resulting in preservation, recovery, and/or regeneration nervous system by interfering with ischemic-triggered cascade. Despite numerous preclinical studies generating promising data several agents, successful bench-to-bedside translations still lacking. present study provides overview current research field treatment. Aside from "traditional" drugs focusing on inflammation, cell death, excitotoxicity, stem-cell-based methods also considered. Furthermore, prospective method using extracellular vesicles that secreted various stem sources, neural cells bone marrow cells, given. review concludes short discussion microbiota-gut-brain axis may serve potential target future therapies.

Language: Английский

Citations

98
Optimizing therapeutic outcomes: preconditioning strategies for MSC-derived extracellular vesicles DOI Creative Commons
Yuqi Song, Fuxin Liang, Weidong Tian

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 10, 2025

Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) are increasingly recognized for their therapeutic potential in regenerative medicine, driven by capabilities immunomodulation tissue repair. However, MSCs present risks such as immunogenic responses, malignant transformation, the to transmit infectious pathogens due intrinsic proliferative differentiative abilities. In contrast, MSC-EVs, particularly exosomes (MSC-exosomes, 30–150 nm diameter), offer a safer profile. These acellular mitigate associated with immune rejection tumorigenesis inherently incapable of forming ectopic tissues, thereby enhancing clinical safety applicability. This review highlights promise MSC-exosomes especially focusing on modulation miRNA (one bioactive molecules MSC-EVs) profiles through various preconditioning strategies exposure hypoxia, chemotherapeutic agents, inflammatory cytokines, physical stimuli. Such conditioning is shown optimize potential. Key miRNAs including miR-21, miR-146, miR-125a, miR-126, miR-181a noted roles facilitating repair modulating responses. functionalities position valuable tool personalized case exosome-based interventions. Despite this also acknowledged limitations traditional MSC therapies advocates strategic pivot towards modalities enhance outcomes. By discussing recent advances detail identifying remaining pitfalls, aims guide future directions improving efficacy MSC-exosome-based therapeutics. Additionally, variability MSC-EVs presents challenges diverse play regulating gene expression cell behavior. The content can be influenced differences isolation purification methods, which may alter specific miRNAs, contributing effects.

Language: Английский

Citations

3
Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke DOI Creative Commons
Jialin He, Jianyang Liu, Yan Huang

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Feb. 26, 2021

Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic are to restore blood flow, which reduce disability but time limited. The interruption flow in contributes intricate pathophysiological processes. Oxidative stress and inflammatory activity two early events the cascade cerebral injury. These factors reciprocal causation directly trigger development autophagy. Appropriate autophagy brain recovery by reducing oxidative activity, while dysfunction aggravates Abundant evidence demonstrates beneficial impact mesenchymal stem cells (MSCs) secretome on MSCs through suppressing reactive oxygen species (ROS) nitrogen (RNS) generation transferring healthy mitochondria damaged cells. Meanwhile, exert anti-inflammation properties production cytokines extracellular vesicles, inhibiting proinflammatory activation, pyroptosis, alleviating blood–brain barrier leakage. Additionally, regulation imbalances gives rise neuroprotection against Altogether, have been promising candidate due their pleiotropic effect.

Language: Английский

Citations

79
Advances in extracellular vesicle functionalization strategies for tissue regeneration DOI Creative Commons
Dandan Zheng, Huitong Ruan, Wei Chen

et al.

Bioactive Materials, Journal Year: 2022, Volume and Issue: 25, P. 500 - 526

Published: Aug. 11, 2022

Extracellular vesicles (EVs) are nano-scale derived by cell secretion with unique advantages such as promoting proliferation, anti-inflammation, blood vessels and regulating differentiation, which benefit their wide applications in regenerative medicine. However, the

Language: Английский

Citations

52
Functional Extracellular Vesicles for Regenerative Medicine DOI
Han Young Kim, Seunglee Kwon, Wooram Um

et al.

Small, Journal Year: 2022, Volume and Issue: 18(36)

Published: March 23, 2022

The unique biological characteristics and promising clinical potential of extracellular vesicles (EVs) have galvanized EV applications for regenerative medicine. Recognized as important mediators intercellular communication, naturally secreted EVs the potential, innate biotherapeutics, to promote tissue regeneration. Although emerged novel therapeutic agents, challenges related transition led further functionalization. In recent years, various engineering approaches such preconditioning, drug loading, surface modification been developed potentiate outcomes EVs. Also, limitations natural addressed by development artificial that offer advantages in terms production yield isolation methodologies. this review, an updated overview current techniques is provided functionalization advances EVs, particularly scope

Language: Английский

Citations

51
Stem cell-derived extracellular vesicles in the therapeutic intervention of Alzheimer's Disease, Parkinson's Disease, and stroke DOI Creative Commons

W. Zhou,

Xudong Wang,

Yumeng Dong

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(8), P. 3358 - 3384

Published: Jan. 1, 2024

With the increase in aging population, occurrence of neurological disorders is rising.Recently, stem cell therapy has garnered attention due to its convenient sourcing, minimal invasiveness, and capacity for directed differentiation.However, there are some disadvantages, such as poor quality control, safety assessments, ethical logistical issues.Consequently, scientists have started shift their from cells extracellular vesicles similar structures properties.Beyond these parallels, can enhance biocompatibility, facilitate easy traversal barriers, minimize side effects.Furthermore, cell-derived be engineered load drugs modify surfaces treatment outcomes.In this review, we summarize functions native vesicles, subsequently review strategies engineering applications Alzheimer's disease, Parkinson's stroke, discuss challenges solutions associated with clinical translation vesicles.

Language: Английский

Citations

9
Oxidative Stress and the Neurovascular Unit DOI Creative Commons
Carmela Rinaldi, Luigi Donato, Simona Alibrandi

et al.

Life, Journal Year: 2021, Volume and Issue: 11(8), P. 767 - 767

Published: July 29, 2021

The neurovascular unit (NVU) is a relatively recent concept that clearly describes the relationship between brain cells and their blood vessels. components of NVU, comprising different types cells, are so interrelated associated with each other they considered as single functioning unit. For this reason, even slight disturbances in NVU could severely affect homeostasis health. In review, we aim to describe current state knowledge concerning role oxidative stress on cell type crosstalk.

Language: Английский

Citations

55
Exosome based miRNA delivery strategy for disease treatment DOI

Zhengwen Fang,

Xinyu Zhang, Hai Huang

et al.

Chinese Chemical Letters, Journal Year: 2021, Volume and Issue: 33(4), P. 1693 - 1704

Published: Nov. 19, 2021

Language: Английский

Citations

54
MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy DOI Creative Commons
Faroogh Marofi,

Kozlitina Iuliia Alexandrovna,

Ria Margiana

et al.

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: Dec. 4, 2021

Abstract Currently, mesenchymal stem/stromal stem cell (MSC) therapy has become a promising option for accelerating cutaneous wound healing. In vivo reports have outlined the robust competences of MSCs to offer solid milieu by inhibition inflammatory reactions, which in turn, enables skin regeneration. Further, due their great potential stimulate angiogenesis and also facilitate matrix remodeling, hold substantial as future therapeutic strategies this context. The MSCs-induced healing is thought mainly rely on secretion myriad paracrine factors addition direct differentiation skin-resident cells. Besides, MSCs-derived exosomes nanoscale closed membrane vesicles recently been suggested an effective cell-free approach support regeneration, circumventing concerns respecting application MSCs. comprise molecular components including lipid, proteins, DNA, microRNA, mRNA, target pathways biological activities recipient cells (e.g., endothelial cell, keratinocyte, fibroblast). secreted exosome modifies macrophage activation, stimulates angiogenesis, instigates keratinocytes dermal fibroblast proliferations well migrations concurrently regulate inherent myofibroblast adjustment turnover ECM. present review, we will focus recent findings concerning derivative with special last decade reports.

Language: Английский

Citations

47