An update on stem cell therapy for stroke patients: Where are we now? DOI
Jonah Gordon, Cesar V. Borlongan

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: 44(9), P. 1469 - 1479

Published: April 19, 2024

With a foundation built upon initial work from the 1980s demonstrating graft viability in cerebral ischemia, stem cell transplantation has shown immense promise promoting survival, enhancing neuroprotection and inducing neuroregeneration, while mitigating both histological behavioral deficits that frequently accompany ischemic stroke. These findings have led to number of clinical trials thoroughly supported strong safety profile for therapy patients but generated variable efficacy. As preclinical evidence continues expand through investigation new lines optimization delivery, it remains critical translational models adhere protocols established basic scientific research. recent shift approach towards utilization cells as conjunctive alongside standard thrombolytic treatments, key issues including timing, route administration, type must each be appropriately translated laboratory order resolve question efficacy ischemia ultimately will enhance therapeutics stroke improving quality life.

Language: Английский

Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review DOI Creative Commons
Ria Margiana, Alexander Markov, Angelina Olegovna Zekiy

et al.

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

Published: July 28, 2022

Abstract The multipotency property of mesenchymal stem cells (MSCs) has attained worldwide consideration because their immense potential for immunomodulation and therapeutic function in tissue regeneration. MSCs can migrate to injury areas contribute immune modulation, secrete anti-inflammatory cytokines hide themselves from the system. Certainly, various investigations have revealed anti-inflammatory, anti-aging, reconstruction, wound healing potentials many vitro vivo models. Moreover, current progresses field biology facilitated progress particular guidelines quality control approaches, which eventually lead clinical application MSCs. In this literature, we provided a brief overview immunoregulatory characteristics immunosuppressive activities addition, discussed enhancement, utilization, responses neural, liver, kidney, bone, heart diseases, healing.

Language: Английский

Citations

230

Mesenchymal stem cell therapy for neurological disorders: The light or the dark side of the force? DOI Creative Commons
Jasmina Isaković,

Klara Šerer,

Barbara Barišić

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 28, 2023

Neurological disorders are recognized as major causes of death and disability worldwide. Because this, they represent one the largest public health challenges. With awareness massive burden associated with these disorders, came recognition that treatment options were disproportionately scarce and, oftentimes, ineffective. To address problems, modern research is increasingly looking into novel, more effective methods to treat neurological patients; which cell-based therapies. In this review, we present a critical analysis features, challenges, prospects stem cell types can be employed numerous disorders—mesenchymal cells (MSCs). Despite fact several studies have already established safety MSC-based approaches, there still some reservations within field regarding their immunocompatibility, heterogeneity, stemness stability, range adverse effects—one tumor-promoting ability. We additionally examine MSCs’ mechanisms action respect in vitro vivo well detail findings past ongoing clinical trials for Parkinson’s Alzheimer’s disease, ischemic stroke, glioblastoma multiforme, multiple sclerosis. Finally, review discusses therapeutics form biomaterials, use electromagnetic fields enhance proliferation differentiation neuronal cells.

Language: Английский

Citations

25

Mesenchymal stem cells and their extracellular vesicle therapy for neurological disorders: traumatic brain injury and beyond DOI Creative Commons
Aref Yarahmadi,

Masoumeh Dorri Giv,

Reza Hosseininejad

et al.

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

Published: Feb. 5, 2025

Traumatic brain injury (TBI) is a complex condition involving mechanisms that lead to dysfunction and nerve damage, resulting in significant morbidity mortality globally. Affecting ~50 million people annually, TBI's impact includes high death rate, exceeding of heart disease cancer. Complications arising from TBI encompass concussion, cerebral hemorrhage, tumors, encephalitis, delayed apoptosis, necrosis. Current treatment methods, such as pharmacotherapy with dihydropyridines, high-pressure oxygen therapy, behavioral non-invasive stimulation, have shown limited efficacy. A comprehensive understanding vascular components essential for developing new treatments improve blood vessel-related damage. Recently, mesenchymal stem cells (MSCs) promising results repairing mitigating Studies indicate MSCs can promote neurogenesis angiogenesis through various mechanisms, including releasing bioactive molecules extracellular vesicles (EVs), which help reduce neuroinflammation. In research, the distinctive characteristics positioned them highly desirable cell sources. Extensive investigations been conducted on regulatory properties their manipulation, tagging, transportation techniques brain-related applications. This review explores progress prospects MSC therapy TBI, focusing action, therapeutic benefits, challenges potential limitations using treating neurological disorders.

Language: Английский

Citations

1

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

30

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

Exosomes Derived From Mesenchymal Stem Cells: Novel Effects in the Treatment of Ischemic Stroke DOI Creative Commons

Yu Xiong,

Jianping Song,

Xinyue Huang

et al.

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: May 2, 2022

Ischemic stroke is defined as an infarction in the brain, caused by impaired cerebral blood supply, leading to local brain tissue ischemia, hypoxic necrosis, and corresponding neurological deficits. At present, revascularization strategies patients with acute ischemic include intravenous thrombolysis mechanical endovascular treatment. However, due short treatment time window (<4.5 h) method restrictions, clinical research focused on new methods treat stroke. Exosomes are nano-sized biovesicles produced endosomal compartment of most eukaryotic cells, containing DNA, complex RNA, protein (30–150 nm). They released into surrounding extracellular fluid upon fusion between multivesicular bodies plasma membrane. have characteristics low immunogenicity, good innate stability, high transmission efficiency, ability cross blood–brain barrier, making them potential therapeutic modalities for The seed sequence miRNA secreted exosomes base-paired complementary mRNA improve microenvironment tissue, thereby regulating downstream signal transduction activities. With exosome still theoretical experimental stages, this review aims shed light derived from mesenchymal stem cells

Language: Английский

Citations

27

The 2021 yearbook of Neurorestoratology DOI Creative Commons

Hari Shanker Sharma,

Michael Chopp, Lin Chen

et al.

Journal of Neurorestoratology, Journal Year: 2022, Volume and Issue: 10(3), P. 100008 - 100008

Published: June 28, 2022

Breakthroughs with rapid changes are the themes of development in Neurorestoratology this year. Given very difficult circumstances persistent COVID-19 pandemic, most colleagues have conducted meaningful research and obtained encouraging results, as described 2020 Yearbook Neurorestoratology. Neurorestorative progress during 2021 depicts recent findings on pathogenesis neurological diseases, neurorestorative mechanisms clinical therapeutic achievements. The risk factors Alzheimer's disease were parts prominent hot topics. Yet, it remains controversial whether β-amyloid accumulation tau protein deposition results of, or reasons for neurodegenerative processes. Neurogenesis is an important mechanism, however, questionable neural stem cells present adult humans brain. Thus, neurogenesis may not derive from endogenous humans. treatments areas efforts these therapies improving quality life patients diseases. There was major exploration cell-based injury. However, unfortunately several multi-center, double-blind observing-blind, placebo controlled, randomized trials mesenchymal stromal products failed to show positive ischemic stroke when employed sub-acute recovery phases there no appreciable differences compared controls. Excitingly, increased numbers investigations brain–computer interface (BCI) reported that showed benefits deficits. In pharmaceutical therapies, Aducanumab (Aduhelm) Sodium Oligomannate approved respectively by United States Food Drug Administration (USFDA) China National Medical Products (NMPA) treat mild-to-moderate disease. Although, decisions approve drugs highly contentious medical scientific community because contradictory other problems associated drug usage. We believe repeating low-level evidence studies negative scanty evidences control little significance. we strongly recommend conducting double-blind, promising innovative methods facilitate their possible translation.

Language: Английский

Citations

27

Safety and Clinical Efficacy of Mesenchymal Stem Cell Treatment in Traumatic Spinal Cord Injury, Multiple Sclerosis and Ischemic Stroke – A Systematic Review and Meta-Analysis DOI Creative Commons
Christopher Elnan Kvistad, Torbjørn Kråkenes, Cecilie Gjerde

et al.

Frontiers in Neurology, Journal Year: 2022, Volume and Issue: 13

Published: May 30, 2022

Background Mesenchymal stem cells (MSCs) is an attractive candidate in regenerative research and clinical trials have assessed their therapeutic potential different neurological conditions with disparate etiologies. In this systematic review, we aimed to assess safety effect of MSC treatment traumatic spinal cord injury (TSCI), multiple sclerosis (MS) ischemic stroke (IS). Methods A search was performed 2021-12-10 MEDLINE, EMBASE, Web Science Cochrane where studies assessing TSCI, MS or IS were included. Studies without control group excluded for efficacy analysis, but included the analysis. For efficacy, AIS score, EDSS score mRS used as endpoints a meta-analysis using random effects model. Findings Of 5,548 identified records, 54 Twenty-six 14 nine IS, which seven, seven five controlled, respectively. There serious adverse events (SAEs), four related surgical procedure one death due complications following implantation MSCs. Three SAEs considered directly all these had transient course. showed no difference conversion from C trend toward more patients treated MSCs improving B compared controls ( p = 0.05). subgroup analysis per protocol, including within 8 weeks after 0.04). there significant differences outcomes between measured by mRS, Interpretation MSC-treatment safe although led fatal outcome TSCI. clear benefit treatment, not necessarily proof inefficacy low number controlled studies. Future should aim do randomized,

Language: Английский

Citations

25

Preclinical assessments of safety and tumorigenicity of very high doses of allogeneic human umbilical cord mesenchymal stem cells DOI Creative Commons
S. Chin, Nik Syazana Saffery, K. Then

et al.

In Vitro Cellular & Developmental Biology - Animal, Journal Year: 2024, Volume and Issue: 60(3), P. 307 - 319

Published: Feb. 29, 2024

Abstract Human umbilical cord-mesenchymal stem cells (hUC-MSCs) have been widely investigated as a new therapeutic agent to treat injuries and inflammatory-mediated autoimmune diseases. Previous studies reported on the safety of low-dose infusion hUC-MSCs, but information cell behaviour at higher doses frequency injection remains uncertain. The aim present study was demonstrate efficacy hUC-MSCs by Cytopeutics® (Selangor, Malaysia) from low an extremely high dose in different monitoring periods healthy BALB/c mice well assessing tumorigenicity B-NDG SCID immunocompromised mice. Umbilical cord two human newborns obtained isolation performed based previous established method. Assessment single or multiple administrations range finding, sub-acute (7 d 28 d) sub-chronic (90 d). Tumorigenicity potential also evaluated for 26 wk. Single up 40 × 10 6 per kilogramme body weight (kg BW) were found no adverse effect terms clinical symptoms, haematology other laboratory parameters, histology examination reduce pro-inflammatory cytokines (IL-6 TNF-α) dose-dependent manner. No sign tumor formation observed 26-wk assessment. administration allogenic safe even very doses, is non-tumorigenic did not cause effects throughout evaluation periods. In addition, exhibited immunomodulatory

Language: Английский

Citations

6

Editing a gateway for cell therapy across the blood–brain barrier DOI Creative Commons
Beatriz Achón Buil, Christian Tackenberg, Ruslan Rust

et al.

Brain, Journal Year: 2022, Volume and Issue: 146(3), P. 823 - 841

Published: Nov. 18, 2022

Abstract Stem cell therapy has been shown to improve stroke outcomes in animal models and is currently advancing towards clinical practice. However, uncertainty remains regarding the optimal route for delivery injured brain. Local intracerebral injections are effective precisely delivering cells into cavity but carry risk of damaging adjacent healthy tissue. Systemic endovascular injections, meanwhile, minimally invasive, most injected do not cross CNS barriers become mechanically trapped peripheral organs. Although blood–brain barrier blood–CSF tightly limit entrance molecules brain parenchyma, immune can these especially under pathological conditions, such as stroke. Deciphering surface signature molecular mechanisms underlying this pathophysiological process holds promise improving targeted systemic In review, we describe experimental approaches that have already developed which (i) either engineered express proteins mimicking infiltrating cells; or (ii) grafts preconditioned with hypoxia incubated pharmacological agents cytokines. Modified be complemented strategies temporarily increase permeability barrier. could significantly enhance homing stem brain, entrapment off-target organs a non-negligible risk. Recent developments safety-switch systems, enable precise elimination transplanted on administration drug, represent promising strategy selectively removing stuck untargeted sum, techniques described review hold great potential substantially efficacy safety future therapies may relevant other diseases.

Language: Английский

Citations

22