Mesenchymal stem cells expressing CES1 and soluble TRAIL activate CPT-11 and induce apoptosis in lung cancer brain metastatic lesions.

To develop a novel therapeutic strategy for lung cancer brain metastases by leveraging the tumor-tropic properties of genetically engineered Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) as vehicles for dual-agent gene therapy across the blood-brain barrier. WJ-MSCs were transiently engineered using lipid nanoparticle (LNP) technology to co-express soluble TRAIL (sTRAIL) and the prodrug-activating enzyme carboxylesterase 1 (CES1). In vitro analyses assessed transfection efficiency, therapeutic protein expression, apoptosis induction, and maintenance of stemness.

Preclinical efficacy and safety assessments of Adult human neural stem cells (AhNSCs) for spinal cord injury.

Spinal cord injury (SCI) is a severe and devastating condition that leads to irreversible damage to neural tissues, creating significant medical, economic, and social challenges. The ability to differentiate into multiple neural cell types and to regulate immune response makes neural stem cells (NSC) a promising strategy for treating SCI. In this study, we investigated the therapeutic potential, safety profile, and tumorigenic risk of intrathecally transplanted adult human neural stem cells (AhNSCs) produced under clinical-grade standards in a Good Manufacturing Practice (GMP) facility, in rat SCI models, thereby laying the foundation for future clinical trials.

Identification of allogeneic and xenogeneic neural stem cells' immunogenicity in the brain and strategies to alleviate transplantation rejection.

Neural stem cells (NSCs) are a promising therapy for central nervous system (CNS) disorders, yet post-transplant immune rejection critically compromises their survival and efficacy. In this study, we demonstrated the neuroinflammatory responses triggered by syngeneic, allogeneic, and xenogeneic NSCs transplantation, and evaluated the immunosuppressive effects of cyclosporine A (CyA) and methylprednisolone (MP) on graft rejection. Our findings revealed that xenogeneic NSCs transplantation induced infiltration of neutrophils (p < 0.

An evolutionarily conserved cation channel tunes the sensitivity of gustatory neurons to ephaptic inhibition in .

In ephaptic coupling, physically adjacent neurons influence one another's activity via the electric fields they generate. To date, the molecular mechanisms that mediate and modulate ephaptic coupling's effects remain poorly understood. Here, we show that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel lateralizes the potentially mutual ephaptic inhibition between gustatory receptor neurons (GRNs).

Therapeutic efficacy of thrombin-preconditioned mesenchymal stromal cell-derived extracellular vesicles on Escherichia coli-induced acute lung injury in mice.

Background: Acute lung injury (ALI) following pneumonia involves uncontrolled inflammation and tissue injury, leading to high mortality. We previously confirmed the significantly increased cargo content and extracellular vesicle (EV) production in thrombin-preconditioned human mesenchymal stromal cells (thMSCs) compared to those in naïve and other preconditioning methods. This study aimed to investigate the therapeutic efficacy of EVs derived from thMSCs in protecting against inflammation and tissue injury in an Escherichia coli (E.

HCN mediates gustatory homeostasis by preserving sensillar transepithelial potential in sweet environments.

Establishing transepithelial ion disparities is crucial for sensory functions in animals. In insect sensory organs called sensilla, a transepithelial potential, known as the sensillum potential (SP), arises through active ion transport across accessory cells, sensitizing receptor neurons such as mechanoreceptors and chemoreceptors. Because multiple receptor neurons are often co-housed in a sensillum and share SP, niche-prevalent overstimulation of single sensory neurons can compromise neighboring receptors by depleting SP.

A Brief Review of Anatomy Education in Korea, Encompassing Its Past, Present, and Future Direction.

Anatomy is a foundational subject in medicine and serves as its language. Hippocrates highlighted its importance, while Herophilus pioneered human dissection, earning him the title of the founder of anatomy. Vesalius later established modern anatomy, which has since evolved historically.

Thrombin Priming Promotes the Neuroprotective Effects of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Via the HGF/AKT/STAT3 Signaling Pathway.

Mesenchymal stem cells (MSCs) directly differentiate into neurons and endothelial cells after transplantation, and their secretome has considerable potential for treating brain injuries. Previous studies have suggested that the effects of MSCs priming with exposure to hypoxia, cytokines, growth factors, or chemical agents could optimize the paracrine potency and therapeutic potential of MSCs. Studies have suggested that thrombin-primed Wharton's Jelly-derived mesenchymal stem cells (Th.

Effects of ethanol washing and storage duration on primary culture of stem cells from human exfoliated deciduous teeth.

Purpose: Since the oral environment harbors various microorganisms, the removal of contaminants during the primary culture process of stem cells from human exfoliated deciduous teeth (SHEDs) is very important. We investigated optimal methods for primary culture of SHEDs with minimal contamination rates.

Materials And Methods: Three different storage conditions for deciduous teeth were utilized:1) storing teeth in Hank's Balanced Salt Solution (HBSS) with 3% penicillin and streptomycin (P/S), 2) storing teeth in HBSS with 3% antibiotics and antimycotics (A-A), and 3) storing teeth in HBSS with A-A, and additional washing with 70% ethanol just before primary culture of dental pulp.

Application of RapidHIT™ ID for cell authentication by fast and convenient STR profiling.

Background: As cell therapies are injected directly into the body, cell authentication is essential. Short tandem repeat (STR) profiling is used for human identification in forensics as well as for cell authentication. The standard methodology (DNA extraction, quantification, polymerase chain reaction, and capillary electrophoresis) takes at least 6 h and requires several instruments to obtain an STR profile.

Dopamine receptor D2 regulates glioblastoma survival and death through MET and death receptor 4/5.

Recent studies indicate that signaling molecules traditionally associated with central nervous system function play critical roles in cancer. Dopamine receptor signaling is implicated in various cancers including glioblastoma (GBM) and it is a recognized therapeutic target, as evidenced by recent clinical trials with a selective dopamine receptor D2 (DRD2) inhibitor ONC201. Understanding the molecular mechanism(s) of the dopamine receptor signaling will be critical for development of potent therapeutic options.

JAK2/STAT3 pathway mediates neuroprotective and pro-angiogenic treatment effects of adult human neural stem cells in middle cerebral artery occlusion stroke animal models.

Mismatches between pre-clinical and clinical results of stem cell therapeutics for ischemic stroke limit their clinical applicability. To overcome these discrepancies, precise planning of pre-clinical experiments that can be translated to clinical trials and the scientific elucidation of treatment mechanisms is important. In this study, adult human neural stem cells (ahNSCs) derived from temporal lobe surgical samples were used (to avoid ethical and safety issues), and their therapeutic effects on ischemic stroke were examined using middle cerebral artery occlusion animal models.

Advances in Neural Stem Cell Therapy for Spinal Cord Injury: Safety, Efficacy, and Future Perspectives.

Spinal cord injury (SCI) is a devastating central nervous system injury that leads to severe disabilities in motor and sensory functions, causing significant deterioration in patients' quality of life. Owing to the complexity of SCI pathophysiology, there has been no effective treatment for reversing neural tissue damage and recovering neurological functions. Several novel therapies targeting different stages of pathophysiological mechanisms of SCI have been developed.

The effects of early exercise in traumatic brain-injured rats with changes in motor ability, brain tissue, and biomarkers.

Traumatic brain injury (TBI) is brain damage which is caused by the impact of external mechanical forces. TBI can lead to the temporary or permanent impairment of physical and cognitive abilities, resulting in abnormal behavior. We recently observed that a single session of early exercise in animals with TBI improved their behavioral performance in the absence of other cognitive abnormalities.

Functional validation of the simplified in vitro 3D Co-culture based BBB model.

Various methods of generating 2D and 3D in vitro blood-brain barrier (BBB) models have previously been published with the objective of developing therapeutics for brain diseases. In general, published methods including our published method demonstrate that in vivo-like semi-permeable barrier can be generated. To further verify that an in vitro BBB model closely represents BBB, functional validation is required.

Simplified in vitro 3D co-culture-based blood-brain barrier model using transwell.

The blood-brain barrier (BBB) is a major hurdle for treatment of brain diseases. To overcome this, precise and reproducible BBB model is one of the key factors for successful evaluation of BBB-penetrating efficacy of developmental drugs. Thus, in vitro BBB model recapitulating the physiological structure of the BBB is a valuable tool for drug discovery and development for brain diseases.

Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats.

Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced efficacy is necessary. This study investigated whether thrombin preconditioning improves the therapeutic efficacy of human Wharton's jelly-derived MSC transplantation for severe neonatal IVH, using a rat model.

Significant Therapeutic Effects of Adult Human Neural Stem Cells for Spinal Cord Injury Are Mediated by Monocyte Chemoattractant Protein-1 (MCP-1).

The limited capability of regeneration in the human central nervous system leads to severe and permanent disabilities following spinal cord injury (SCI) while patients suffer from no viable treatment option. Adult human neural stem cells (ahNSCs) are unique cells derived from the adult human brain, which have the essential characteristics of NSCs. The objective of this study was to characterize the therapeutic effects of ahNSCs isolated from the temporal lobes of focal cortical dysplasia type IIIa for SCI and to elucidate their treatment mechanisms.

Combination stem cell therapy using dental pulp stem cells and human umbilical vein endothelial cells for critical hindlimb ischemia.

Narrowing of arteries supplying blood to the limbs provokes critical hindlimb ischemia (CLI). Although CLI results in irreversible sequelae, such as amputation, few therapeutic options induce the formation of new functional blood vessels. Based on the proangiogenic potentials of stem cells, in this study, it was examined whether a combination of dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) could result in enhanced therapeutic effects of stem cells for CLI compared with those of DPSCs or HUVECs alone.

Effects of Long-Term In Vitro Expansion on Genetic Stability and Tumor Formation Capacity of Stem Cells.

Stem cell therapeutics are emerging as novel alternative treatments for various neurodegenerative diseases based on their regenerative potentials. However, stem cell transplantation might have side effects such as tumor formation that limit their clinical applications. Especially, in vitro expansion of stem cells might provoke genetic instability and tumorigenic potential.

Adult Human Multipotent Neural Cells Could Be Distinguished from Other Cell Types by Proangiogenic Paracrine Effects via MCP-1 and GRO.

Adult human multipotent neural cells (ahMNCs) are unique cells derived from adult human temporal lobes. They show multipotent differentiation potentials into neurons and astrocytes. In addition, they possess proangiogenic capacities.

Challenging Microvascular Decompression Surgery for Hemifacial Spasm.

Objective: Microvascular decompression (MVD) is the most effective treatment for hemifacial spasm (HFS). However, surgical difficulties due to complex anatomy or revision surgery can endanger the functional integrity of the brainstem. We describe surgically challenging cases and provide operative guidance that may be helpful for neurosurgeons who perform MVDs.

Optimal Preclinical Conditions for Using Adult Human Multipotent Neural Cells in the Treatment of Spinal Cord Injury.

Stem cell-based therapeutics are amongst the most promising next-generation therapeutic approaches for the treatment of spinal cord injury (SCI), as they may promote the repair or regeneration of damaged spinal cord tissues. However, preclinical optimization should be performed before clinical application to guarantee safety and therapeutic effect. Here, we investigated the optimal injection route and dose for adult human multipotent neural cells (ahMNCs) from patients with hemorrhagic stroke using an SCI animal model.