Layer-specific sensory processing impairment in the primary somatosensory cortex after motor cortex infarction DOI Creative Commons

Atsushi Fukui,

Hironobu Osaki, Yoshifumi Ueta

et al.

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Feb. 28, 2020

Abstract Primary motor cortex (M1) infarctions sometimes cause sensory impairment. Because signals play a vital role in control, impairment compromises the recovery and rehabilitation of disability. However, neural mechanism is poorly understood. We show that processing mouse primary somatosensory (S1) was impaired acute phase M1 recovered layer-specific manner subacute phase. This layer-dependent process anatomical connection pattern from to S1 suggested functional connectivity plays key A simulation study demonstrated loss inhibition could impair S1, compensation for recover temporal coding. Consistently, optogenetic activation suppressed sustained response S1. Taken together, we revealed how focal stroke alters cortical network activity processing, which inhibitory input may be involved.

Language: Английский

Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): a first-in-human, open-label intervention study DOI
Lisanne M. Baak, Nienke Wagenaar, Niek E. van der Aa

et al.

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 21(6), P. 528 - 536

Published: May 11, 2022

Language: Английский

Citations

76
Mesenchymal stem cell therapy for ischemic stroke: A look into treatment mechanism and therapeutic potential DOI
Junsheng Li, Qian Zhang, Wen Wang

et al.

Journal of Neurology, Journal Year: 2020, Volume and Issue: 268(11), P. 4095 - 4107

Published: Aug. 6, 2020

Language: Английский

Citations

92
Mesenchymal Stem Cells as a Cornerstone in a Galaxy of Intercellular Signals: Basis for a New Era of Medicine DOI Open Access
Silvia Fernández-Francos, Noemí Eiró, Luis A. Costa

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(7), P. 3576 - 3576

Published: March 30, 2021

Around 40% of the population will suffer at some point in their life a disease involving tissue loss or an inflammatory autoimmune process that cannot be satisfactorily controlled with current therapies. An alternative for these processes is represented by stem cells and, especially, mesenchymal (MSC). Numerous preclinical studies have shown MSC to therapeutic effects different clinical conditions, probably due mesodermal origin. Thereby, appear play central role control galaxy intercellular signals anti-inflammatory, regenerative, angiogenic, anti-fibrotic, anti-oxidative stress anti-apoptotic, anti-tumor, anti-microbial type. This concept forces us return origin natural physiological as starting understand evolution therapy field regenerative medicine. These biological effects, demonstrated countless studies, justify first applications, and draw horizon new strategies. However, several limitations cell are recognized, such safety issues, handling difficulties purposes, high economic cost. For reasons, there ongoing tendency consider use MSC-derived secretome products tool, since they reproduce parent cells. it necessary resolve key aspects, choice ideal type according each indication implementation standardized production Therefore, science based on intelligently designed derivative able advance towards innovative more personalized medical biotechnology.

Language: Английский

Citations

79
Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges DOI Creative Commons
Weifeng Li, Linli Shi, Bei Hu

et al.

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

Published: Feb. 9, 2021

Stroke, the most prevalent cerebrovascular disease, causes serious loss of neurological function and is leading cause morbidity mortality worldwide. Despite advances in pharmacological surgical therapy, treatment for functional rehabilitation following stroke limited with a consequent impact on quality life. Over past decades, mesenchymal stem cell (MSCs)-based therapy has emerged as novel strategy various diseases including due to their unique properties that include easy isolation, multipotent differentiation potential strong paracrine capacity. Although MSCs have shown promising results stroke, there remain many challenges overcome prior therapeutic application. In this review, we focus issues: scientific data from preclinical studies clinical trials stroke; mechanisms underlying MSC-based related timing delivery MSC senescence.

Language: Английский

Citations

72
Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial DOI Creative Commons
Elena de Celis, Blanca Fuentes, María Alonso de Leciñana

et al.

Cell Transplantation, Journal Year: 2022, Volume and Issue: 31

Published: Jan. 1, 2022

Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent promising innovative strategy focused on reduction neurologic sequelae by enhancement brain plasticity. We performed phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe (National Institutes Health Stroke Scale [NIHSS] 8–20) were randomized (1:1) receive intravenous adipose tissue–derived mesenchymal stem (AD-MSCs) or placebo within the first 2 weeks onset. The primary outcome was safety, evaluating adverse events (AEs), and systemic complications, tumor development. secondary evaluated treatment efficacy measuring modified Rankin (mRS), NIHSS, infarct size, blood biomarkers. report final trial results after 24 months follow-up. Recruitment began December 2014 stopped 2017 19 20 planned patients included. Six did not study treatment: two due technical issues four for acquiring exclusion criteria randomization. sample composed 13 (4 receiving AD-MSCs 9 placebo). One patient group died week delivery sepsis. Two non-treatment-related serious AEs occurred AD-MSC nine group. total number complications similar between groups. No injection-related registered, nor At follow-up, showed nonsignificantly lower median NIHSS score (interquartile range, 3 [3–5.5] vs 7 [0–8]). Neither had differences mRS scores throughout follow-up visits up month 24. Therefore, from safe at

Language: Английский

Citations

57
Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications DOI Creative Commons
Benjamin V. Ineichen, Eva Furrer, Servan Grüninger

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(6), P. e3002667 - e3002667

Published: June 13, 2024

There is an ongoing debate about the value of animal experiments to inform medical practice, yet there are limited data on how well therapies developed in studies translate humans. We aimed assess 2 measures translation across various biomedical fields: (1) The proportion which transition from human application, including involved timeframes; and (2) consistency between study results. Thus, we conducted umbrella review, English systematic reviews that evaluated animals Medline, Embase, Web Science Core Collection were searched inception until August 1, 2023. assessed therapeutic interventions advancing any study, a randomized controlled trial (RCT), regulatory approval. meta-analyzed concordance studies. risk bias was probed using 10-item checklist for reviews. included 122 articles, describing 54 distinct diseases 367 interventions. Neurological focus 32% overall progressing 50% studies, 40% RCTs, 5% Notably, our meta-analysis showed 86% positive results clinical median times 5, 7, 10 years reach RCT, approval, respectively. conclude that, contrary widespread assertions, rate successful animal-to-human may be higher than previously reported. Nonetheless, low final approval indicates potential deficiencies design both early trials. To ameliorate efficacy translating bench bedside, advocate enhanced robustness reinforcement generalizability.

Language: Английский

Citations

12
The Role of Nanomaterials in Stroke Treatment: Targeting Oxidative Stress DOI Creative Commons
Guini Song, Min Zhao, Han‐Min Chen

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Stroke has a high rate of morbidity and disability, which seriously endangers human health. In stroke, oxidative stress leads to further damage the brain tissue. Therefore, treatment for is urgently needed. However, antioxidative drugs have demonstrated obvious protective effects in preclinical studies, but clinical studies not seen breakthroughs. Nanomaterials, with their characteristically small size, can be used deliver excellent performance treating various diseases. Additionally, some nanomaterials shown potential scavenging reactive oxygen species (ROS) stroke according nature nanomaterials. The drugs’ delivery ability great significance translation application antioxidants. It increases drug blood concentration half‐life targets ischemic protect cells from stress‐induced death. This review summarizes characteristics progress antioxidant therapy including hemorrhagic neural regeneration. We also discuss prospect challenges application, such as toxicity off‐target

Language: Английский

Citations

43
Mesenchymal Stem/Stromal Cell Therapy in Blood–Brain Barrier Preservation Following Ischemia: Molecular Mechanisms and Prospects DOI Open Access
Phuong Thao,

Chung-Che Wu,

Yung‐Hsiao Chiang

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(18), P. 10045 - 10045

Published: Sept. 17, 2021

Ischemic stroke is the leading cause of mortality and long-term disability worldwide. Disruption blood–brain barrier (BBB) a prominent pathophysiological mechanism, responsible for series subsequent inflammatory cascades that exacerbate damage to brain tissue. However, benefit recanalization limited in most patients because narrow therapeutic time window. Recently, mesenchymal stem cells (MSCs) have been assessed as excellent candidates cell-based therapy cerebral ischemia, including neuroinflammatory alleviation, angiogenesis neurogenesis promotion through their paracrine actions. In addition, accumulating evidence on how MSC preserves BBB integrity after may open up novel targets treating cerebrovascular diseases. this review, we focus molecular mechanisms MSC-based ischemia-induced prevention compromise. Currently, effects MSCs are primarily based fundamental pathogenesis breakdown, such attenuating leukocyte infiltration, matrix metalloproteinase (MMP) regulation, antioxidant, anti-inflammation, stabilizing morphology crosstalk between cellular components BBB. We also discuss prospective studies improve effectiveness enhanced migration into defined regions cells. Targeted promising new direction being prioritized extensive research.

Language: Английский

Citations

41
Potential mechanisms and therapeutic targets of mesenchymal stem cell transplantation for ischemic stroke DOI Creative Commons
Li Zhou, Huimin Zhu, Xue Bai

et al.

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 12, 2022

Ischemic stroke is one of the major causes death and disability in world. Currently, most patients cannot choose intravenous thrombolysis or intravascular mechanical thrombectomy because narrow therapeutic windows severe complications. Stem cell transplantation an emerging treatment has been studied various central nervous system diseases. Animal clinical studies showed that mesenchymal stem cells (MSCs) could alleviate neurological deficits bring hope for ischemic treatment. This article reviewed biological characteristics, safety, feasibility efficacy MSCs therapy, potential targets MSCs, production process Good Manufacturing Practices-grade to explore use provide new directions stroke.

Language: Английский

Citations

29
Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles DOI Creative Commons
Jiahao Song, Da Zhou, Lili Cui

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 22, 2024

Abstract Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window associated risks underscore necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as promising therapeutic approach due to ability modulate post-stroke microenvironment facilitate neuroprotection neurorestoration. This review synthesizes current research on potential stem EVs AIS, focusing origin, biogenesis, mechanisms action, strategies enhancing targeting capacity efficacy. Additionally, we explore innovative combination therapies discuss both challenges prospects EV-based treatments. Our findings reveal that exhibit diverse effects such promoting neuronal survival, diminishing neuroinflammation, protecting blood-brain barrier, angiogenesis neurogenesis. Various strategies, including modifications cargo modifications, been developed improve efficacy EVs. Combining other treatments, therapy, cell transplantation, nanomedicine, gut microbiome modulation, holds great promise improving outcomes. However, heterogeneity need standardized protocols EV production quality control remain be addressed. represent avenue offering address limitations Further needed optimize translate benefits clinical practice, an emphasis ensuring safety, overcoming regulatory hurdles, specificity delivery target tissues. Graphical

Language: Английский

Citations

7