Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 21, 2025
Language: Английский
Journal of Biomedical Science, Journal Year: 2021, Volume and Issue: 28(1)
Published: April 13, 2021
Abstract Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy because of their high immunomodulation ability, tropism towards inflamed and injured tissues, easy access isolation. Currently, there more than 1200 registered MSC clinical trials globally. However, lack standardized methods to characterize cell safety, efficacy, biodistribution dramatically hinders the progress utility in practice. In this review, we summarize current state MSC-based therapy, focusing on systemic safety MSCs. MSC-associated risks tumor initiation promotion underlying mechanisms these discussed. addition, methodology pharmacokinetics pharmacodynamics therapies addressed. Better understanding MSCs will facilitate future applications precision medicine using stem cells.
Language: Английский
Citations
188
Cell & Bioscience, Journal Year: 2020, Volume and Issue: 10(1)
Published: Sept. 22, 2020
Spinal cord injury (SCI) is the damage to spinal that can lead temporary or permanent loss of function due nerve. The SCI patients are often associated with poor quality life.This review discusses current status mesenchymal stem cell (MSC) therapy for SCI, criteria considering application MSC and novel biological therapies be applied together MSCs enhance its efficacy. Bone marrow-derived (BMSCs), umbilical cord-derived (UC-MSCs) adipose tissue-derived (ADSCs) have been trialed treatment SCI. Application may minimize secondary protect neural elements survived initial mechanical insult by suppressing inflammation. Additionally, shown differentiate into neuron-like cells stimulate proliferation rebuild damaged nerve tissue.These characteristics crucial restoration upon as has limited regenerative capacity it also something cannot achieved pharmacological physiotherapy interventions. New including secretome therapy, immunotherapy scaffolds combined therapeutic effects.
Language: Английский
Citations
169
Bone Research, Journal Year: 2022, Volume and Issue: 10(1)
Published: April 8, 2022
Spinal cord injury (SCI) leads to loss of motor and sensory function below the level imposes a considerable burden on patients, families, society. Repair injured spinal has been recognized as global medical challenge for many years. Significant progress made in research pathological mechanism injury. In particular, with development gene regulation, cell sequencing, tracing technologies, in-depth explorations SCI microenvironment have become more feasible. However, translational studies related repair not yielded significant results. This review summarizes latest two aspects pathology: intraneuronal imbalance regenerative imbalance. We also strategies based imbalance, including medications, transplantation, exosomes, tissue engineering, reprogramming, rehabilitation. The current state future directions are discussed. combined, precise, multitemporal strategy repairing is potential direction.
Language: Английский
Citations
140
ACS Nano, Journal Year: 2022, Volume and Issue: 16(7), P. 10811 - 10823
Published: July 5, 2022
Revascularization treatment is a critical measure for tissue engineering therapies like spinal cord repair. As multipotent stem cells, mesenchymal cells (MSCs) have proven to regulate the lesion microenvironment through feedback signals. The angiogenic capacities of MSCs been reported be facilitated by vein endothelial in niche. emerging evidence demonstrated roles exosomes cell-cell and cell-microenvironment communications, cope with ischemia complication traumatic injury, study extracts factors stimulate using (EX) derived from hypoxic preconditioned (HPC) human umbilical (HUVEC). HPC hypoxia time segment only 15 min efficiently enhanced function EX facilitating angiogenesis activity. stimulated HPC-EX showed significant tube formation within 2 h, vivo transplantation elicited effective nerve repair after rat transection, which could attributed pro-angiogenic anti-inflammatory impacts MSCs. Through simulation HPC-tailored HUVEC exosomes, results proposed an efficient strategy injury provide inspiration based on exosomes.
Language: Английский
Citations
81
Cells, Journal Year: 2023, Volume and Issue: 12(6), P. 853 - 853
Published: March 9, 2023
Spinal cord injury (SCI) is a complex tissue resulting in permanent and degenerating damage to the central nervous system (CNS). Detrimental cellular processes occur after SCI, including axonal degeneration, neuronal loss, neuroinflammation, reactive gliosis, scar formation. The glial border forms segregate neural lesion isolate spreading inflammation, oxygen species, excitotoxicity at epicenter preserve surrounding healthy tissue. physicochemical barrier composed of elongated astrocytes, fibroblasts, microglia secreting chondroitin sulfate proteoglycans, collogen, dense extra-cellular matrix. While this physiological response preserves viable tissue, it also detrimental regeneration. To overcome negative outcomes associated with formation, therapeutic strategies have been developed: prevention resolution developed scar, cell transplantation into lesion, endogenous reprogramming. This review focuses on cellular/molecular aspects discusses advantages disadvantages promote regeneration SCI.
Language: Английский
Citations
77
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Feb. 24, 2023
Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting regeneration release neuro-nutrients, are a promising strategy for treatment of SCI. Preclinical studies shown that MSCs promote sensory motor function recovery in rats. In clinical trials, been reported improve American Injury Association (ASIA) scores. However, effectiveness treating patients remains controversial. tumorigenesis ensuring survival hostile environment challenging. this article we examine evidence pathophysiological changes occurring after We then review underlying mechanisms summarize potential application practice. Finally, highlight challenges surrounding use discuss future applications.
Language: Английский
Citations
53
Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)
Published: Feb. 16, 2023
Abstract Background Limited progress in terms of an effective treatment for spinal cord injury (SCI) emphasizes the urgent need novel therapies. As a vital central nervous system component, resident astrocytes play crucial roles regulating recovery after SCI. In this study, SCI was compared following transplantation either A1 or A2 astrocytes. are harmful as they upregulate neurotoxic classical complement cascade genes. Conversely, characterized neuroprotective production many neurotrophic factors. Methods We used different supernatant obtained from microglia stimulated with lipopolysaccharide interleukin-4 to generate and detected influence on neurons by co-culturing neurons. transplanted into lesion site assessed progression, neural restoration, glia formation locomotor recovery. Results Astrocytes were polarized phenotypes culture interleukin-4, respectively. Furthermore, significantly suppressed glutamate-induced neuronal apoptosis promoted degree neuron arborization. Transplantation these mice improved motor function recovery, preserved spared supraspinal pathways, decreased scar deposition, increased neurofilament at Additionally, enhanced potentially beneficial A2-like genes also group. Moreover, luxol fast blue staining electron microscopy indicated preservation myelin organized structure than Conclusions astrocyte could be promising potential therapy Graphical
Language: Английский
Citations
43
Brain, Journal Year: 2023, Volume and Issue: 146(7), P. 2672 - 2693
Published: Feb. 24, 2023
Abstract Spinal cord injury (SCI) is an as yet untreatable neuropathology that causes severe dysfunction and disability. Cell-based therapies hold neuroregenerative neuroprotective potential, but, although being studied in SCI patients for more than two decades, long-term efficacy safety remain unproven, which cell types result higher neurological functional recovery remains under debate. In a comprehensive scoping review of 142 reports registries cell-based clinical trials, we addressed the current therapeutical trends critically analysed strengths limitations studies. Schwann cells, olfactory ensheathing cells (OECs), macrophages various stem have been tested, well combinations these other cells. A comparative analysis between reported outcomes each type was performed, according to gold-standard outcome measures like ASIA impairment scale, motor sensory scores. Most trials were early phases development (phase I/II), involved with complete chronic injuries traumatic aetiology did not display randomized control arm. Bone marrow OECs most commonly tested while open surgery injection main methods delivering into spinal or submeningeal spaces. Transplantation support such resulted highest Impairment Scale (AIS) grade conversion rates (improvements ∼40% transplanted patients), surpassed spontaneous improvement rate expected within 1 year post-injury (5–20%). Some peripheral blood-isolated neural offer potential improving patient recovery. Complementary treatments, particularly post-transplantation rehabilitation regimes, may contribute highly However, unbiased comparisons are difficult draw, given great heterogeneity design used how reported. It therefore crucial standardize when aiming value evidence-based conclusions.
Language: Английский
Citations
43
Journal of Advanced Research, Journal Year: 2024, Volume and Issue: 70, P. 103 - 124
Published: May 9, 2024
Mesenchymal stem cell (MSC)-based therapies have yielded beneficial effects in a broad range of preclinical models and clinical trials for human diseases. In the context MSC transplantation, it is widely recognized that main mechanism regenerative potential MSCs not their differentiation, with vivo data revealing transient low engraftment rates. Instead, therapeutic are mainly attributed to its secretome, i.e., paracrine factors secreted by these cells, further offering more attractive innovative approach due effectiveness safety cell-free product. this review, we will discuss benefits MSC-derived secretome medicine particular focus on respiratory, hepatic, neurological Both free vesicular be detailed. We also address novel strategies capable improving healing potential, namely delivering important molecules according specific diseases tissue needs, as well non-clinical studies allow us dissect mechanisms action. includes both soluble non-soluble factors, organized extracellular vesicles (EVs). Importantly, besides depending origin, characteristics deeply influenced external stimuli, highlighting possibility optimizing through preconditioning approaches. Nevertheless, clarity around action remains ambiguous, whereas need standardized procedures successful translation those products clinics urges.
Language: Английский
Citations
26
Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)
Published: Aug. 26, 2024
Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role the paracrine effects mesenchymal stem cells (MSCs) have emerged as promising therapeutic approach for SCI. Thus, this study aimed evaluate safety potential intrathecal administration allogeneic exosomes derived from human umbilical MSCs (HUC-MSCs) patients complete subacute This was single-arm, open-label, phase I clinical trial 12-month follow-up period. HUC-MSCs were extracted tissue, isolated via ultracentrifugation. After injection, each participant underwent evaluation, including neurological assessment using American Spinal Injury Association (ASIA) scale, Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) NBD score, modified Ashworth scale (MAS), lower urinary tract function questionnaire. Nine SCI recruited. The injection HUC-MSCs-exosomes safe well tolerated. No early or late adverse event (AE) attributable intervention observed. Significant improvements ASIA pinprick (P-value = 0.039) light touch 0.038) scores, SCIM III total score 0.027), 0.042) also at after compared baseline. demonstrated that is Moreover, it seems therapy might be associated these patients. In regard, future larger II/III trials adequate power highly required. Iranian Registry Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .
Language: Английский
Citations
18