The Application of Brain Organoid Technology in Stroke Research: Challenges and Prospects DOI Creative Commons
Guini Song, Min Zhao, Han‐Min Chen

et al.

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

Published: June 21, 2021

Stroke is a neurological disease responsible for significant morbidity and disability worldwide. However, there remains dearth of effective therapies. The failure many therapies stroke in clinical trials has promoted the development human cell-based models, such as brain organoids. Brain organoids differ from pluripotent stem cells that they recapitulate various key features central nervous system (CNS) three-dimensional (3D) space. Recent studies have demonstrated could serve new platform to study diseases. are several limitations, scarcity glia vasculature organoids, which important studying stroke. Herein, we summarized application organoid technology research, modeling transplantation purposes. We also discuss methods overcome limitations technology, well future prospects its research. Although difficulties challenges associated with it clear this approach will play critical role exploration treatment.

Language: Английский

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials DOI Creative Commons
Zhonghao Li,

Xiaoke Dong,

Min Tian

et al.

Stem Cell Research & Therapy, Journal Year: 2020, Volume and Issue: 11(1)

Published: June 26, 2020

Abstract Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stroke. Our was registered on PROSPERO ( http://www.crd.york.ac.uk/PROSPERO ), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database Systematic Reviews, Central Register Controlled Trials), Web Science (Science Citation Index Expanded) relevant studies up to 31 May 2019. We included clinical trials which compared outcomes (measured by National Institutes Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) (such as death adverse effects) between control in performed random effect meta-analysis using Review Manager 5.3. nine randomized controlled (RCTs) seven non-randomized (NRSs), involving 740 participants. Stem were associated with better measured NIHSS (mean difference (MD) − 1.63, 95% confidence intervals (CI) 2.73 0.53, I 2 =60%) BI (MD 14.68, CI 1.12 28.24, = 68%) RCTs, 6.40, 3.14 9.65, 0%) NRSs. However, risk bias high RCTs heterogeneity. There no significant mortality cell group group. Fever, headache, recurrent most frequently reported effects. shows that can improve neurological deficits activities daily living patients

Language: Английский

Citations

54
The effects of intravenous infusion of autologous mesenchymal stromal cells in patients with subacute middle cerebral artery infarct: a phase 2 randomized controlled trial on safety, tolerability and efficacy DOI
Zhe Kang Law, Hui Jan Tan, S. Chin

et al.

Cytotherapy, Journal Year: 2021, Volume and Issue: 23(9), P. 833 - 840

Published: May 12, 2021

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
Non-human primate models of focal cortical ischemia for neuronal replacement therapy DOI
Jiao Mu, Peng Hao, Hongmei Duan

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 43(9), P. 1456 - 1474

Published: May 31, 2023

Despite the high prevalence, stroke remains incurable due to limited regeneration capacity in central nervous system. Neuronal replacement strategies are highly diverse biomedical fields that attempt replace lost neurons by utilizing exogenous stem cell transplants, biomaterials, and direct neuronal reprogramming. Although these approaches have achieved encouraging outcomes mostly rodent model, further preclinical validation non-human primates (NHP) is still needed prior clinical trials. In this paper, we briefly review recent progress of promising therapy NHP studies. Moreover, summarize key characteristics as valuable translational tools discuss (1) species their advantages terms genetics, physiology, neuroanatomy, immunology, behavior; (2) various methods for establishing focal ischemic models study regenerative plastic changes associated with motor functional recovery; (3) a comprehensive analysis experimentally clinically accessible potential adaptive mechanism. Our specifically aims facilitate selection appropriate cortical efficient prognostic evaluation research design strategies.

Language: Английский

Citations

20
Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy DOI Creative Commons
Leonidas D Panos, Panagiotis Bargiotas, Marcel Arnold

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 991 - 1006

Published: March 1, 2024

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally.This review offers detailed analysis stem cell applications stroke (ischemic and hemorrhagic) recovery.It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), Granulocyte-Colony Stimulating Factor (G-CSF) focusing types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear (BMMSCs), Neural Stem/Progenitor (NSCs).The paper compiles clinical trial data to evaluate effectiveness safety addresses the ethical concerns these innovative treatments.By explaining mechanisms cell-induced neurological repair, this underscores cells' potential revolutionizing rehabilitation suggests avenues future research.

Language: Английский

Citations

7
Neurorestorative Approaches for Ischemic Stroke DOI Creative Commons

Paulina Michór,

Lydia Renardson,

Shen Li

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 550, P. 69 - 78

Published: May 17, 2024

Despite recent advances in acute stroke management, most patients experiencing a will suffer from residual brain damage and functional impairment. Addressing those deficits would require neurorestoration, i.e., rebuilding tissue to repair the structural caused by stroke. However, there are major pathobiological, anatomical technological hurdles making neurorestorative approaches remarkably challenging, true neurorestoration after larger ischemic lesions could not yet be achieved. On other hand, has been steady advancement our understanding of limits regeneration adult mammalian as well fundamental organization growth during embryo- ontogenesis. This paralleled development novel animal models study stroke, biomaterials that can used support stem cell technologies. review gives detailed explanation so far preventing achievement It also describe concepts advancements biomaterial science, organoid culturing, modeling may enable investigation post-stroke translationally relevant setups. Finally, achievements experimental studies have potential starting point research activities eventually bring within reach.

Language: Английский

Citations

7
Brain repair mechanisms after cell therapy for stroke DOI Creative Commons
Ruslan Rust, Lina R. Nih, Luca Liberale

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3286 - 3305

Published: June 25, 2024

Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, underlying mechanisms by which they promote remain unclear. Here, we briefly review endogenous ischaemic stroke then focus on how different stem progenitor sources can repair. Specifically, examine transplanted grafts contribute to improved functional recovery either through direct replacement or stimulating pathways. Additionally, discuss recently implemented refinement methods, such as preconditioning, microcarriers, genetic safety switches universal (immune evasive) transplants, well therapeutic potential these pharmacologic manipulations further enhance efficacy therapies. By gaining a deeper understanding post-ischaemic mechanisms, prospective trials may be refined advance post-stroke therapy clinic.

Language: Английский

Citations

6
Erythropoietin Abrogates Post-Ischemic Activation of the NLRP3, NLRC4, and AIM2 Inflammasomes in Microglia/Macrophages in a TAK1-Dependent Manner DOI Creative Commons
Ole Heinisch, Thomas Zeyen, Tobias Goldmann

et al.

Translational Stroke Research, Journal Year: 2021, Volume and Issue: 13(3), P. 462 - 482

Published: Oct. 9, 2021

Inflammasomes are known to contribute brain damage after acute ischemic stroke (AIS). TAK1 is predominantly expressed in microglial cells and can regulate the NLRP3 inflammasome, but its impact on other inflammasomes including NLRC4 AIM2 AIS remains elusive. EPO has been shown reduce protein levels different disease models. Whether EPO-mediated neuroprotection conveyed via an EPO/TAK1/inflammasome axis microglia be clarified. Subjecting mice deficient for microglia/macrophages (Mi/MΦ) revealed a significant reduction infarct sizes neurological impairments compared corresponding controls. Post-ischemic increased activation of TAK1, NLRP3, NLRC4, their associated downstream cascades were markedly reduced upon deletion Mi/MΦ TAK1. administration improved clinical outcomes dampened stroke-induced inflammasome cascades, which was not evident Pharmacological inhibition BV-2 did influence post-OGD IL-1β levels, suggesting compensatory activities among inflammasomes. Overall, we provide evidence that regulates expression Furthermore, mitigated inflammasomes, indicating might mediated axis.

Language: Английский

Citations

28
Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke DOI Creative Commons

Satoru Yabuno,

Takao Yasuhara,

Takayuki Nagase

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 24, 2023

Abstract Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. this study, we aimed to clarify whether combination of intracerebral human modified bone marrow-derived MSCs, SB623 cells, and voluntary running wheel (RW) exert synergistic therapeutic effects on rat model ischemic stroke. Methods Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary (Ex) groups were trained in cage RW from day 7 before MCAO. cells (4.0 × 10 5 cells/5 μl) stereotactically injected into the striatum at 1 after Behavioral tests performed 1, 7, 14 MCAO using Neurological Severity Score (mNSS) cylinder test. Rats euthanized 15 mRNA level evaluation infarct area, endogenous neurogenesis, angiogenesis, expression brain-derived neurotrophic factor (BDNF) vascular endothelial growth (VEGF). The randomly assigned one four groups: vehicle, Ex, SB623, + Ex groups. Results group achieved significant recovery mNSS compared vehicle ( p < 0.05). area was significantly decreased those all other number BrdU/Doublecortin (Dcx) double-positive subventricular zone (SVZ) dentate gyrus (DG), laminin-positive boundary (IBZ), BDNF VEGF increased Conclusions This study suggests that achieves robust synergistically promotes neurogenesis angiogenesis ischemia, possibly through mechanism involving up-regulation VEGF.

Language: Английский

Citations

11
Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca2+ -ATPase Isoform1 DOI Creative Commons
Jialin He, Jianyang Liu, Yan Huang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Oct. 30, 2020

Olfactory mucosa mesenchymal stem cells (OM-MSCs) have exhibited their effectiveness in central nervous system diseases and provided an appealing candidate for the treatment of ischemic stroke. Previous evidence showed that Golgi apparatus (GA) secretory-pathway Ca2+-transport ATPases isoform1 (SPCA1) was a potential therapeutic target In this study, we explored neuroprotective mechanism OM-MSCs its effect on expression function SPCA1 during cerebral ischemia/reperfusion. Based vitro vivo experiments, discovered attenuated apoptosis oxidative stress stroke models, reduced infarction volume improved neurologic deficits rats. also upregulated alleviated Ca2+ overload, decreased edema dissolution GA neurons. Moreover, depletion OGD/R treated N2a mitigated protective effects OM-MSCs. Altogether, exerted probably via modulating reducing

Language: Английский

Citations

29