Perspectives on Stem Cell Therapy in Diabetic Neuropathic Pain.

Diabetes mellitus-related morbidity and mortality are primarily caused by long-term complications such as retinopathy, nephropathy, cardiomyopathy, and neuropathy. Diabetic neuropathy (DN) involves the progressive degeneration of axons and nerve fibers due to chronic exposure to hyperglycemia. This metabolic disturbance leads to excessive activation of the glycolytic pathway, inducing oxidative stress and mitochondrial dysfunction, ultimately resulting in nerve damage.

Mesenchymal stem cell- and extracellular vesicle-based therapies for Alzheimer's disease: progress, advantages, and challenges.

Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis.

Gangliosides in nervous system development, regeneration, and pathologies.

Gangliosides, sialic acid-containing sphingolipids, are major constituents of neuronal membranes. According to the number of sialic acids and the structure of the oligosaccharide chain, gangliosides can be classified as simple or complex and grouped in different ganglio-series. Hundreds of gangliosides have been identified in vertebrate cells, with different expression patterns during development and related to several physiological processes, especially in the nervous system.

Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases.

Neurological disorders include a wide spectrum of clinical conditions affecting the central and peripheral nervous systems. For these conditions, which affect hundreds of millions of people worldwide, generally limited or no treatments are available, and cell-based therapies have been intensively investigated in preclinical and clinical studies. Among the available cell types, mesenchymal stem/stromal cells (MSCs) have been widely studied but as yet no cell-based treatment exists for neurological disease.

Hyperacute transplantation of umbilical cord mesenchymal stromal cells in a model of severe intracerebral hemorrhage.

Aim: Intracerebral hemorrhage (ICH) has limited therapeutic options. We have shown that an intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) 24 h after an ICH in rats reduced the residual hematoma volume after a moderate hemorrhage but was inefficient in severe ICH. Here, we investigated whether a treatment in the hyperacute phase would be more effective in severe ICH.

Mesenchymal Stem Cell Therapy in Diabetic Cardiomyopathy.

The incidence and prevalence of diabetes mellitus (DM) are increasing worldwide, and the resulting cardiac complications are the leading cause of death. Among these complications is diabetes-induced cardiomyopathy (DCM), which is the consequence of a pro-inflammatory condition, oxidative stress and fibrosis caused by hyperglycemia. Cardiac remodeling will lead to an imbalance in cell survival and death, which can promote cardiac dysfunction.

Chromosomal aberrations after induced pluripotent stem cells reprogramming.

Induced pluripotent stem cells (iPSCs) are generated from adult cells that have been reprogrammed to pluripotency. However, in vitro cultivation and genetic reprogramming increase genetic instability, which could result in chromosomal abnormalities. Maintenance of genetic stability after reprogramming is required for possible experimental and clinical applications.

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases.

Stem cell therapy is a promising alternative approach to heart diseases. The most prevalent source of multipotent stem cells, usually called somatic or adult stem cells (mesenchymal stromal/stem cells, MSCs) used in clinical trials is bone marrow (BM-MSCs), adipose tissue (AT-MSCs), umbilical cord (UC-MSCs) and placenta. Therapeutic use of MSCs in cardiovascular diseases is based on the benefits in reducing cardiac fibrosis and inflammation that compose the cardiac remodeling responsible for the maintenance of normal function, something which may end up causing progressive and irreversible dysfunction.

GD3 synthase deletion alters retinal structure and impairs visual function in mice.

Gangliosides are glycosphingolipids abundantly expressed in the vertebrate nervous system, and are classified into a-, b-, or c-series according to the number of sialic acid residues. The enzyme GD3 synthase converts GM3 (an a-series ganglioside) into GD3, a b-series ganglioside highly expressed in the developing and adult retina. The present study evaluated the visual system of GD3 synthase knockout mice (GD3s ), morphologically and functionally.

Signaling pathways modulated by monocular enucleation in the superior colliculus of juvenile rats.

Monocular eye enucleation (ME) is a classical paradigm to induce neural plasticity in retinal ganglion cells (RGCs) axons from the intact eye, especially when performed within the critical period of visual system development. However, the precise mechanisms underlying the axonal sprouting and synaptogenesis seen in this model remain poorly understood. In the present work, we investigated the temporal alterations in phosphorylation of three kinases related to axonal growth and synaptogenesis-GSK3β (an important repressor of axonal outgrowth), AKT, and ERK-in superior colliculus of rats submitted to ME during early postnatal development.

Human mesenchymal stem cell therapy promotes retinal ganglion cell survival and target reconnection after optic nerve crush in adult rats.

Background: Optic-nerve injury results in impaired transmission of visual signals to central targets and leads to the death of retinal ganglion cells (RGCs) and irreversible vision loss. Therapies with mesenchymal stem cells (MSCs) from different sources have been used experimentally to increase survival and regeneration of RGCs.

Methods: We investigated the efficacy of human umbilical Wharton's jelly-derived MSCs (hWJ-MSCs) and their extracellular vesicles (EVs) in a rat model of optic nerve crush.

Therapeutic Benefit of the Association of Lodenafil with Mesenchymal Stem Cells on Hypoxia-induced Pulmonary Hypertension in Rats.

Pulmonary arterial hypertension (PAH) is characterized by the remodeling of pulmonary arteries, with an increased pulmonary arterial pressure and right ventricle (RV) overload. This work investigated the benefit of the association of human umbilical cord mesenchymal stem cells (hMSCs) with lodenafil, a phosphodiesterase-5 inhibitor, in an animal model of PAH. Male Wistar rats were exposed to hypoxia (10% O) for three weeks plus a weekly i.

Modeling ALS using iPSCs: is it possible to reproduce the phenotypic variations observed in patients ?

Amyotrophic lateral sclerosis (ALS) is a fatal disease that leads to progressive degeneration of motoneurons. Mutations in the , , and genes, among others, have been associated with ALS. Although motoneuron degeneration is the common outcome of ALS, different pathological mechanisms seem to be involved in this process, depending on the genotypic background of the patient.

Intravenous Human Umbilical Cord-Derived Mesenchymal Stromal Cell Administration in Models of Moderate and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggest mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared with other disorders such as ischemic stroke.

Generation of patient-specific pluripotent induced stem cell line UFRJi007-A from a Brazilian familial amyotrophic lateral sclerosis patient.

Induced pluripotent stem cell (iPSC) line were generated from erythroblasts of a Brazilian patient with familiar form of amyotrophic lateral sclerosis (ALS). NGS analysis demonstrated that patient carried a mutation in SOD1 gene, as well as a deletion in FUS gene. CytoTune™-iPS 2.

Generation of four patient-specific pluripotent induced stem cell lines from two Brazilian patients with amyotrophic lateral sclerosis and two healthy subjects.

Induced pluripotent stem cell (iPSC) lines were generated from erythroblasts of two patients with amyotrophic lateral sclerosis (ALS) and two healthy individuals. One familial and one sporadic ALS patients were used, both with genetic alterations in VAPB gene. CytoTune™-iPS 2.

Long-term neuronal survival, regeneration, and transient target reconnection after optic nerve crush and mesenchymal stem cell transplantation.

Background: Retina and/or optic nerve injury may cause irreversible blindness, due to degeneration of retinal ganglion cells. We and others have previously shown that the intravitreal injection of mesenchymal stem cells (MSCs) protects injured retinal ganglion cells and stimulates their regeneration after optic nerve injury, but the long-term effects of this therapy are still unknown.

Methods: We injected rat MSC (rMSC) intravitreally in adult (3-5 months) Lister Hooded rats of either sex after optic nerve crush.

Human Mesenchymal Stem Cell Therapy Reverses Su5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Mice.

Pulmonary arterial hypertension (PAH) is a disease characterized by an increase in pulmonary vascular resistance and right ventricular (RV) failure. We aimed to determine the effects of human mesenchymal stem cell (hMSC) therapy in a SU5416/hypoxia (SuH) mice model of PAH. C57BL/6 mice (20-25 g) were exposure to 4 weeks of hypoxia combined vascular endothelial growth factor receptor antagonism (20 mg/kg SU5416; weekly injections; PAH mice).

Monocular denervation of visual nuclei modulates APP processing and sAPPα production: A possible role on neural plasticity.

Amyloid precursor protein (APP) is essential to physiological processes such as synapse formation and neural plasticity. Sequential proteolysis of APP by beta- and gamma-secretases generates amyloid-beta peptide (Aβ), the main component of senile plaques in Alzheimer Disease. Alternative APP cleavage by alpha-secretase occurs within Aβ domain, releasing soluble α-APP (sAPPα), a neurotrophic fragment.