Stem cell and intranasal

BACKGROUND: Neonatal encephalopathy following hypoxia-ischemia (HI) is a leading cause of childhood death and morbidity. Hypothermia (HT), the only available but obligatory therapy is limited due to a short therapeutic window and limited efficacy. An adjuvant therapy overcoming limitations of HT is still missing. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have shown promising therapeutic effects in various brain injury models. Challenges associated with MSCs' heterogeneity and senescence can be mitigated by the use of EVs from clonally expanded immortalized MSCs (ciMSCs)...

Memory problems are often the first signs of cognitive impairment related to Alzheimer's disease (AD), and stem cells and stem cell-derived exosomes (EXOs) have been studied for their therapeutic potential to improve the disease signs. While many studies have shown the anti-inflammatory and immunomodulatory effects of stem cells and exosomes on improving memory in different AD models, there is still insufficient data to determine how they modulate neural plasticity to enhance spatial memory and learning ability...

Intranasal administration is a promising strategy to enhance the delivery of the sEVsomes-based drug delivery system to the central nervous system (CNS). This study aimed to explore central distributive characteristics of mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) and underlying pathways. Here, we observed that intranasal MSC-sEVs were rapidly distributed to various brain regions, especially in the subcortex distant from the olfactory bulb, and were absorbed by multiple cells residing in these regions...

BACKGROUND: Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute treatment options for perinatal stroke are limited supportive care, such as controlling hypoglycemia and seizures. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. Preclinical findings have culminated in ongoing human neonatal studies. OBJECTIVES: To evaluate the benefits and harms of stem cell-based interventions for the treatment of stroke in newborn infants compared to control (placebo or no treatment) or stem-cell based interventions of a different type or source...

Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. Intranasal administration of GPC-EV to Wistar rats for 6 days improved sensorimotor functions assessed over a 14-day observation period...

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, resulting in gradual destruction of cognitive abilities. Research on the development of various AD treatments is underway; however, no definitive treatment has been developed yet. Herein, we present induced pluripotent stem cell (iPSC)-derived cortical neural stem cell secretome (CNSC-SE) as a new treatment candidate for AD and explore its efficacy. METHODS: We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation...

Gene therapy has great potential in treating neurodegenerative diseases with complex pathologies. The combination of small interfering RNAs (siRNAs) targeting β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and caspase-3 will provide an effective treatment option for Alzheimer's disease (AD). To overcome the multiple physiological barriers and improve the therapeutic efficacy of siRNAs, lesion-recognizing nanoparticles (NPs) are constructed in this study for the synergistic treatment of AD...

BACKGROUND: Morphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse. The morphine-induced increases in neuroinflammation, brain oxidative stress, and alteration of glutamate levels in the hippocampus and nucleus accumbens have been associated with morphine dependence and a higher severity of withdrawal symptoms...

AIMS: Epidermal Neural Crest Stem Cells (EPI-NCSCs) have emerged as prospective ideal candidates to meet the fundamental requirements of cell-based therapies in neurodegenerative disorders. The present study aimed to identify the potential of metformin in driving EPI-NCSCs to neuronal/glial differentiation and express neurotrophic factors as well as assess their therapeutic potential for mitigating the main behavioral manifestations of chemotherapy-induced neurotoxicity (CIN). MAIN METHODS: EPI-NCSCs were extracted from the bulge region of hair follicle...

Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to fatal outcomes for subgroups of patients with pre-existing co-morbidities. We previously reported a significant association between high expression levels of a cancer stem cell protein, doublecortin-like kinase 1 (DCLK1), in the lungs and macrophages of SARS-CoV-2-infected patients and the severity of coronavirus disease 2019 (COVID-19). Herein, we demonstrate a pivotal role of DCLK1 in the viral replication cycle and the dysregulation of cell signaling that contributes to SARS-CoV-2 pathology...

BACKGROUND: There have been no effective treatments for slowing or reversing Alzheimer's disease (AD) until now. Growing preclinical evidence, including this study, suggests that mesenchymal stem cells-secreted exosomes (MSCs-Exos) have the potential to cure AD. AIMS: The first three-arm, drug-intervention, phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos (ahaMSCs-Exos) in patients with mild to moderate AD...

Efficacious stem cell-based therapies for traumatic brain injury (TBI) depend on successful delivery, migration, and engraftment of stem cells to induce neuroprotection. L-myc expressing human neural stem cells (LMNSC008) demonstrate an inherent tropism to injury sites after intranasal (IN) administration. We hypothesize that IN delivered LMNSC008 cells migrate to primary and secondary injury sites and modulate biomarkers associated with neuroprotection and tissue regeneration. To test this hypothesis, immunocompetent adult female rats received either controlled cortical impact injury or sham surgery...

Parkinson's disease (PD) is a neurodegenerative disorder with motor deficits due to nigrostriatal dopamine depletion and with the non-motor/premotor symptoms (NMS) such as anxiety, cognitive dysfunction, depression, hyposmia, and sleep disorders. NMS is presented in at least one-fifth of the patients with PD. With the histological information being investigated, stem cells are shown to provide neurotrophic supports and cellular replacement in the damaging brain areas under PD conditions. Pathological change of progressive PD includes degeneration and loss of dopaminergic neurons in the substantia nigra of the midbrain...

Efficacious stem cell-based therapies for traumatic brain injury (TBI) depend on successful delivery, migration, and engraftment of stem cells to induce neuroprotection. L-myc expressing human neural stem cells (LMNSC008) demonstrate an inherent tropism to injury sites after intranasal (IN) administration. We hypothesize that IN delivered LMNSC008 cells migrate to primary and secondary injury sites and modulate biomarkers associated with neuroprotection and tissue regeneration. To test this, immunocompetent adult female rats received a controlled cortical impact injury (CCI) or sham surgery...

Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB), potentially exacerbating nerve damage and emphasizing the criticality of preserving the BSCB integrity during SCI treatment. This study explores an alternative therapeutic approach for SCI by identifying a subpopulation of exosomes with stable BSCB function and achieving a specific targeted delivery. Specific subpopulations of CD146+ CD271+ umbilical cord mesenchymal stem cells (UCMSCs) were isolated, from which engineered exosomes (RGD-CD146+ CD271+ UCMSC-Exos) with targeted neovascularization function were obtained through gene transfection...

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The use of nucleic acids to treat various brain diseases could offer new therapeutic modalities, providing the nucleic acids may be effectively delivered to areas of the brain using non-toxic vectors. In this study, we present evidence that genes may be successfully delivered in a dose-dependent manner via the nose, primarily to the cerebral cortex using a 6-O-glycolchitosan (GC) formulation of plasmid DNA. Positively charged (zeta potential = +13 - + 25 mV) GC-DNA nanoparticles of 100 - 500 nm in diameter with favourable cell biocompatibility were shown to deliver the reporter Green Fluorescent Protein (GFP) plasmid to the U87MG cell line and the resulting protein expression was not significantly different from that obtained with Lipofectamine 2000...

INTRODUCTION: Extracellular vesicles (EVs) released by human-induced pluripotent stem cell (hiPSC)-derived neural stem cells (NSCs) have robust antiinflammatory and neurogenic properties due to therapeutic miRNAs and proteins in their cargo. Hence, hiPSC-NSC-EVs are potentially an excellent biologic for treating neurodegenerative disorders, including Alzheimer's disease (AD). METHODS: This study investigated whether intranasally (IN) administered hiPSC-NSC-EVs would quickly target various neural cell types in the forebrain, midbrain, and hindbrain regions of 3-month-old 5xFAD mice, a model of β-amyloidosis and familial AD...

Neurological injuries can have numerous debilitating effects on functional status including sensorimotor deficits, cognitive impairment, and behavioral symptoms. Despite the disease burden, treatment options remain limited. Current pharmacological interventions are targeted at symptom management but are ineffective in reversing ischemic brain damage. Stem cell therapy for ischemic brain injury has shown promising preclinical and clinical results and has attracted attention as a potential therapeutic option...