T-cadherin modulates adipogenic differentiation in mesenchymal stem cells: insights into ligand interactions.

Introduction: T-cadherin, a non-canonical member of the cadherin superfamily, was initially identified for its involvement in homophilic recognition within the nervous and vascular systems. Apart from its adhesive function, T-cadherin acts as a receptor for two ligands: LDL, contributing to atherogenic processes, and HMW adiponectin, a hormone with well-known cardiovascular protective properties. However, the precise role of T-cadherin in adipose tissue remains elusive.

Mesenchymal stem/stromal cells alleviate early-stage pulmonary fibrosis in a uPAR-dependent manner.

Pulmonary fibrosis, a debilitating lung disorder characterised by excessive fibrous tissue accumulation in lung parenchyma, compromises respiratory function leading to a life-threatening respiratory failure. While its origins are multifaceted and poorly understood, the urokinase system, including urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plays a significant role in regulating fibrotic response, extracellular matrix remodelling, and tissue repair. Mesenchymal stem/stromal cells (MSCs) hold promise in regenerative medicine for treating pulmonary fibrosis.

Novel Immortalized Human Multipotent Mesenchymal Stromal Cell Line for Studying Hormonal Signaling.

Multipotent mesenchymal stromal cells (MSCs) integrate hormone and neuromediator signaling to coordinate tissue homeostasis, tissue renewal and regeneration. To facilitate the investigation of MSC biology, stable immortalized cell lines are created (e.g.

Peripheral 5-HT/HTR6 axis is responsible for obesity-associated hypertension.

Hypertension is one of the major life-threatening complications of obesity. Recently adipose multipotent mesenchymal stromal cells (MSCs) were implicated to the pathogenesis of obesity-associated hypertension. These cells amplify noradrenaline-induced vascular cell contraction via cAMP-mediated signaling pathway.

T-Cadherin Deficiency Is Associated with Increased Blood Pressure after Physical Activity.

T-cadherin is a regulator of blood vessel remodeling and angiogenesis, involved in adiponectin-mediated protective effects in the cardiovascular system and in skeletal muscles. GWAS study has previously demonstrated a SNP in the gene to be associated with hypertension. However, the role of T-cadherin in regulating blood pressure has not been experimentally elucidated.

Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension.

Hypertension is a major risk factor for cardiovascular diseases, such as strokes and myocardial infarctions. Nearly 70% of hypertension onsets in adults can be attributed to obesity, primarily due to sympathetic overdrive and the dysregulated renin-angiotensin system. Sympathetic overdrive increases vasoconstriction via α1-adrenoceptor activation on vascular cells.

Metabolic and Body Composition Changes in Ice Hockey Players Using an Ergogenic Drug (Cytoflavin).

Background And Objectives: In ice hockey, the major physical workload comes from acceleration in all planes of motion and transitions between skating trajectories. Hockey players' anthropometric characteristics correlate with performance. In team sports, the use of ergogenic drugs for recovery is relevant to avoid athletes' overtraining.

New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies.

Topical advances in studying molecular and cellular mechanisms responsible for regeneration in the peripheral nervous system have highlighted the ability of the nervous system to repair itself. Still, serious injuries represent a challenge for the morphological and functional regeneration of peripheral nerves, calling for new treatment strategies that maximize nerve regeneration and recovery. This review presents the canonical view of the basic mechanisms of nerve regeneration and novel data on the role of exosomes and their transferred microRNAs in intracellular communication, regulation of axonal growth, Schwann cell migration and proliferation, and stromal cell functioning.

Decreased Insulin Sensitivity in Telomerase-Immortalized Mesenchymal Stem Cells Affects Efficacy and Outcome of Adipogenic Differentiation .

Modern biomedical science still experiences a significant need for easy and reliable sources of human cells. They are used to investigate pathological processes underlying disease, conduct pharmacological studies, and eventually applied as a therapeutic product in regenerative medicine. For decades, the pool of adult mesenchymal stem/stromal cells (MSCs) remains a promising source of stem and progenitor cells.

Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair.

Gene therapy is one of the promising approaches for regenerative medicine. Local and long-term expression of essential growth factors allows to achieve the desired therapeutic effect. However, some aspects of prolonged usage of genetic constructs encoding growth factors, such as toxicity, mutagenicity, genotoxicity, and ability to disseminate from the injection site and mediate ectopic expression of therapeutic proteins, are poorly investigated.

Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells.

Multipotent stromal cells (MSC) demonstrate remarkable functional heterogeneity; however, its molecular mechanisms remain largely obscure. In this study, we explored MSC response to hormones, which activate Gs-protein / cyclic AMP (cAMP) / protein kinase A (PKA) dependent signaling, at the single cell level using genetically encoded biosensor PKA-Spark. For the first time, we demonstrated that about half of cultured MSCs are not able to activate the cAMP/PKA pathway, possibly due to the limited availability of adenylyl cyclases.

Three-Dimensional Model of Dorsal Root Ganglion Explant as a Method of Studying Neurotrophic Factors in Regenerative Medicine.

Neurotrophiс factors play a key role in the development, differentiation, and survival of neurons and nerve regeneration. In the present study, we evaluated the effect of certain neurotrophic factors (NGF, BDNF, and GDNF) on axon growth and migration of Nestin-green fluorescent protein (GFP)-positive cells using a 3D model of dorsal root ganglion (DRG) explant culture in Matrigel. Our method generally represents a convenient model for assessing the effects of soluble factors and therapeutic agents on axon growth and nerve regeneration in R&D studies.

Downregulation of uPAR promotes urokinase translocation into the nucleus and epithelial to mesenchymal transition in neuroblastoma.

The urokinase system is involved in a variety of physiological processes, such as fibrinolysis, matrix remodeling, wound healing, and regeneration. Upon binding to its cognate receptor urokinase-type plasminogen activator receptor (uPAR), urokinase-type plasminogen activator (uPA) catalyzes the conversion of plasminogen to plasmin and the activation of matrix metalloproteases. Apart from this, uPA-uPAR interaction can lead to the activation of transcription factors, mitogen-activated protein kinase signaling pathways and RTK cascades.

Angiotensin receptor subtypes regulate adipose tissue renewal and remodelling.

Obesity is often associated with high systemic and local renin-angiotensin system (RAS) activity in adipose tissue. Adipose-derived mesenchymal stem/stromal cells (ADSCs), responsible for adipose tissue growth upon high-fat diet, express multiple angiotensin II receptor isoforms, including angiotensin II type 1 receptor (AT R), angiotensin II type 2 receptor (AT R), Mas and Mas-related G protein-coupled receptor D. Although AT R is expressed on most ADSCs, other angiotensin receptors are co-expressed on a small subpopulation of the cells, a phenomenon that results in a complex response pattern.

Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K channels.

The current knowledge of electrogenesis in mesenchymal stromal cells (MSCs) remains scarce. Earlier, we demonstrated that in MSCs from the human adipose tissue, transduction of certain agonists involved the phosphoinositide cascade. Its pivotal effector PLC generates DAG that can regulate ion channels directly or via its derivatives, including arachidonic acid (AA).

Noradrenaline Sensitivity Is Severely Impaired in Immortalized Adipose-Derived Mesenchymal Stem Cell Line.

Primary adipose tissue-derived multipotent stem/stromal cells (adMSCs) demonstrate unusual signaling regulatory mechanisms, i.e., increased of sensitivity to catecholamines in response to noradrenaline.

Flow cytometry analysis of adrenoceptors expression in human adipose-derived mesenchymal stem/stromal cells.

Mesenchymal stem/stromal cells (MSCs) were identified in most tissues of an adult organism. MSCs mediate physiological renewal, as well as regulation of tissue homeostasis, reparation and regeneration. Functions of MSCs are regulated by endocrine and neuronal signals, and noradrenaline is one of the most important MSC regulators.

Coupling of P2Y receptors to Ca mobilization in mesenchymal stromal cells from the human adipose tissue.

The purinergic transduction was examined in mesenchymal stromal cells (MSCs) from the human adipose tissue, and several nucleotides, including ATP, UTP, and ADP, were found to mobilize cytosolic Ca. Transcripts for multiple purinoreceptors were detected in MSC preparations, including A, A, A, P2Y, P2Y, P2Y, P2Y, P2Y, P2Y, P2Y, P2X, P2X, and P2X. Cellular responses to nucleotides were insignificantly sensitive to bath Ca, pointing at a minor contribution of Ca entry, and were suppressed by U73122 and 2-APB, implicating the phosphoinositide cascade in coupling P2Y receptors to Ca release.

Data supporting that adipose-derived mesenchymal stem/stromal cells express angiotensin II receptors in situ and in vitro.

This article contains results of analyses of angiotensin II receptors expression in human adipose tissue and stem/stromal cells isolated from adipose tissue. We also provide here data regarding the effect of angiotensin II on intracellular calcium mobilization in adipose tissue derived stem/stromal cells (ADSCs). Discussion of the data can be found in (Sysoeva et al.

Local angiotensin II promotes adipogenic differentiation of human adipose tissue mesenchymal stem cells through type 2 angiotensin receptor.

Obesity is often associated with high systemic and local activity of renin-angiotensin system (RAS). Mesenchymal stem cells of adipose tissue are the main source of adipocytes. The aim of this study was to clarify how local RAS could control adipose differentiation of human adipose tissue derived mesenchymal stem cells (ADSCs).

Calcium-gated K channels of the K1.1- and K3.1-type couple intracellular Ca signals to membrane hyperpolarization in mesenchymal stromal cells from the human adipose tissue.

Electrogenesis in mesenchymal stromal cells (MSCs) remains poorly understood. Little is known about ion channels active in resting MSCs and activated upon MSC stimulation, particularly, by agonists mobilizing Ca in the MSC cytoplasm. A variety of Ca-gated ion channels may couple Ca signals to polarization of the plasma membrane.

Activation of β-adrenergic receptors is required for elevated α1A-adrenoreceptors expression and signaling in mesenchymal stromal cells.

Sympathetic neurons are important components of mesenchymal stem cells (MSCs) niche and noradrenaline regulates biological activities of these cells. Here we examined the mechanisms of regulation of MSCs responsiveness to noradrenaline. Using flow cytometry, we demonstrated that α1A adrenergic receptors isoform was the most abundant in adipose tissue-derived MSCs.

Urokinase and urokinase receptor participate in regulation of neuronal migration, axon growth and branching.

Purpose: Recent findings indicate the significant contribution of urokinase and urokinase receptor (uPA and uPAR) in the processes of nerve regeneration, however, their role in axonal growth and branching is unclear. Using a 3D model of mouse Dorsal Root Ganglia (DRG) explants, differentiated into neurons Neuro 2a cells and transgenic mice lacking the urokinase gene, we studied the involvement of the uPA/uPAR system in the neural cell migration, neurite outgrowth, elongation and branching.

Results: uPA and uPAR are expressed in the growth cones of axons.

Characterization of secretomes provides evidence for adipose-derived mesenchymal stromal cells subtypes.

Introduction: This study was aimed at deciphering the secretome of adipose-derived mesenchymal stromal cells (ADSCs) cultured in standard and hypoxic conditions to reveal proteins, which may be responsible for regenerative action of these cells.

Methods: Human ADSCs were isolated from 10 healthy donors and cultured for 3-4 passages. Cells were serum deprived and cell purity was assessed using multiple cell surface markers.