Extracellular vesicle therapy in neurological disorders.

Extracellular vesicles (EVs) are vital for cell-to-cell communication, transferring proteins, lipids, and nucleic acids in various physiological and pathological processes. They play crucial roles in immune modulation and tissue regeneration but are also involved in pathogenic conditions like inflammation and degenerative disorders. EVs have heterogeneous populations and cargo, with numerous subpopulations currently under investigations.

Cellular and Noncellular Approaches for Repairing the Damaged Blood-CNS-Barrier in Amyotrophic Lateral Sclerosis.

Numerous reports have demonstrated the breakdown of the blood-CNS barrier (B-CNS-B) in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Re-establishing barrier integrity in the CNS is critical to prevent further motor neuron degeneration from harmful components in systemic circulation. Potential therapeutic strategies for repairing the B-CNS-B may be achieved by the replacement of damaged endothelial cells (ECs) via stem cell administration or enhancement of endogenous EC survival through the delivery of bioactive particles secreted by stem cells.

Facing the Challenges in the COVID-19 Pandemic Era: From Standard Treatments to the Umbilical Cord-Derived Mesenchymal Stromal Cells as a New Therapeutic Strategy.

Coronavirus disease 2019 (COVID-19), the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which counts more than 650 million cases and more than 6.6 million of deaths worldwide, affects the respiratory system with typical symptoms such as fever, cough, sore throat, acute respiratory distress syndrome (ARDS), and fatigue. Other nonpulmonary manifestations are related with abnormal inflammatory response, the "cytokine storm", that could lead to a multiorgan disease and to death.

Transplanted Human Bone Marrow Endothelial Progenitor Cells Prolong Functional Benefits and Extend Survival of ALS Mice Likely via Blood-Spinal Cord Barrier Repair.

Amyotrophic lateral sclerosis (ALS) is a multifactorial disease with one of these factors being an impaired blood-spinal cord barrier (BSCB). In order to block harmful components in systemic circulation from accessing the CNS, barrier damage needs alleviation. Recently, we found that symptomatic ALS animals treated with intravenously delivered human bone marrow-derived CD34+ (hBM34+) cells or endothelial progenitor cells (hBMEPCs) showed delayed disease progression for 4 weeks post-transplant via BSCB repair.

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway.

Background: Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats.

Getting the guts to expand stroke treatment: The potential for microbiome targeted therapies.

Aims: This review focuses on the recent literature regarding the role of the gut-brain axis (GBA) following ischemic stroke.

Discussion: Stroke is the 5th leading cause of death and disability in the United States; however, few therapies have been developed to improve prognoses. There is a plethora of evidence suggesting peripheral inflammatory responses play a large role in the pathogenesis of stroke.

Patching Up the Permeability: The Role of Stem Cells in Lessening Neurovascular Damage in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a debilitating disease with poor prognosis. The pathophysiology of ALS is commonly debated, with theories involving inflammation, glutamate excitotoxity, oxidative stress, mitochondria malfunction, neurofilament accumulation, inadequate nutrients or growth factors, and changes in glial support predominating. These underlying pathological mechanisms, however, act together to weaken the blood brain barrier and blood spinal cord barrier, collectively considered as the blood central nervous system barrier (BCNSB).

Inflammatory gut as a pathologic and therapeutic target in Parkinson's disease.

Parkinson's disease (PD) remains a significant unmet clinical need. Gut dysbiosis stands as a PD pathologic source and therapeutic target. Here, we assessed the role of the gut-brain axis in PD pathology and treatment.

Sequestration of Inflammation in Parkinson's Disease via Stem Cell Therapy.

Parkinson's disease is the second most common neurodegenerative disease. Insidious and progressive, this disorder is secondary to the gradual loss of dopaminergic signaling and worsening neuroinflammation, affecting patients' motor capabilities. Gold standard treatment includes exogenous dopamine therapy in the form of levodopa-carbidopa, or surgical intervention with a deep brain stimulator to the subcortical basal ganglia.

Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats.

Aims: SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke.

Methods: We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group.

Multinuclear MRI Reveals Early Efficacy of Stem Cell Therapy in Stroke.

Compromised adult human mesenchymal stem cells (hMSC) can impair cell therapy efficacy and further reverse ischemic recovery. However, in vitro assays require extended passage to characterize cells, limiting rapid assessment for therapeutic potency. Multinuclear magnetic resonance imaging and spectroscopy (MRI/S) provides near real-time feedback on disease progression and tissue recovery.

The Role of Concomitant Nrf2 Targeting and Stem Cell Therapy in Cerebrovascular Disease.

Despite the reality that a death from cerebrovascular accident occurs every 3.5 min in the United States, there are few therapeutic options which are typically limited to a narrow window of opportunity in time for damage mitigation and recovery. Novel therapies have targeted pathological processes secondary to the initial insult, such as oxidative damage and peripheral inflammation.

Apolipoprotein A1 Enhances Endothelial Cell Survival in an Model of ALS.

Altered lipoprotein metabolism is considered a pathogenic component of amyotrophic lateral sclerosis (ALS). Apolipoprotein A1 (ApoA1), a major high-density lipoprotein (HDL) protein, is associated with prevention of vascular damage. However, ApoA1's effects on damaged endothelium in ALS are unknown.

Exosomes Derived From Mesenchymal Stem Cells Pretreated With Ischemic Rat Heart Extracts Promote Angiogenesis via the Delivery of DMBT1.

Mesenchymal stem cell-derived exosomes (MSC-Exos) have been shown to promote angiogenesis. Treating MSCs with ischemic rat brain extracts was sufficient to augment their benefits in stroke. However, no similar analyses of ischemic heart extracts have been performed to date.

Effects of Lovastatin on Brain Cancer Cells.

Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for brain tumors includes surgery, radiotherapy, and chemotherapy. However, resistance to treatment remains a problem with recurrence shortly following.

Unveiling the mechanisms of hematopoietic stem cell transplantation: Balancing cell senescence and proliferation in cancer and beyond.

In a recent Nature Medicine publication, Sailor et al. elucidate the complex mechanism of hematopoietic stem cell transplantation (HSCT) and chemotherapy, highlighting the occurrence of host microglia senescence coupled with donor macrophage engraftment. These findings warrant a more in-depth understanding of HSCT and its adjunctive therapies to enhance current and future treatments for cancer and a plethora of pro-inflammatory disorders.

Neuroinflammation, Stem Cells, and Stroke.

Stroke remains a significant unmet clinical need with few treatment options that have a very narrow therapeutic window, thereby causing massive mortality and morbidity in the United States and around the world. Accordingly, finding safe and effective novel treatments with a wider therapeutic window stands as an urgent need in stroke. The progressive inflammation that occurs centrally and peripherally after stroke serves as a unique therapeutic target to retard and even halt the secondary cell death.

Contraceptive drug, Nestorone, enhances stem cell-mediated remodeling of the stroke brain by dampening inflammation and rescuing mitochondria.

Ischemic stroke remains a significant unmet need causing massive mortality and morbidity due to few treatment options with limited therapeutic window. The progestin Nestorone® (segesterone acetate) displays high affinity for the progesterone receptor in exerting its potent birth control and hormone replacement therapy. Accumulating evidence implicates a new utility of Nestorone in affording neuroprotection in a variety of central nervous system diseases, including stroke.

Mesenchymal Stromal Cells in Ischemic Brain Injury.

Ischemic brain injury represents a major cause of death worldwide with limited treatment options with a narrow therapeutic window. Accordingly, novel treatments that extend the treatment from the early neuroprotective stage to the late regenerative phase may accommodate a much larger number of stroke patients. To this end, stem cell-based regenerative therapies may address this unmet clinical need.

Lovastatin Inhibits RhoA to Suppress Canonical Wnt/β-Catenin Signaling and Alternative Wnt-YAP/TAZ Signaling in Colon Cancer.

Statins are first-line drugs used to control patient lipid levels, but there is recent evidence that statin treatment can lower colorectal cancer (CRC) incidence by 50% and prolong CRC patient survival through mechanisms that are poorly understood. In this study, we found that the treatment of APC mice by the mevalonate pathway inhibitor lovastatin significantly reduced the number of colonic masses and improved hypersplenism and peripheral anemia. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) analysis of colonic mass tissues showed a potent inhibitory effect in both Wnt/β-catenin signaling and YAP/TAZ signaling in the lovastatin treatment group.

Gut-Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders.

Human lifestyle and dietary behaviors contribute to disease onset and progression. Neurodegenerative diseases (NDDs), considered multifactorial disorders, have been associated with changes in the gut microbiome. NDDs display pathologies that alter brain functions with a tendency to worsen over time.

A review of the pathology and treatment of TBI and PTSD.

This literature review focuses on the underlying pathophysiology of TBI and PTSD symptoms, while also examining the plethora of stem cell treatment options to ameliorate these neuronal and functional changes. As more veterans return suffering from TBI and/or PTSD, it is vital that researchers discover novel therapies to mitigate the detrimental symptoms of both diagnoses. A variety of stem cell treatments have been studied and offer hopeful options for TBI and PTSD recovery.

Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1 T.

Extended therapeutic application remains a significant issue in the use of stem cell therapies to treat ischemic stroke. Along these lines, neurological recovery in a rodent model of ischemic stroke was evaluated following implantation of human mesenchymal stem cell aggregates (hMSC-agg), labeled with micron-sized particles of iron oxide, directly into the lateral ventricle contralateral to the ischemic lesion hemisphere. Longitudinally, disease progression and response to hMSC-agg therapy were assessed by H and Na magnetic resonance imaging (MRI) at 21.