Conductive Hydrogel Restores Electrical Conduction to Promote Neurological Recovery in a Rat Model.

Spinal cord injury (SCI), caused by significant physical trauma, as well as other pathological conditions, results in electrical signaling disruption and loss of bodily functional control below the injury site. Conductive biomaterials have been considered a promising approach for treating SCI, owing to their ability to restore electrical connections between intact spinal cord portions across the injury site. In this study, we evaluated the ability of a conductive hydrogel, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), to restore electrical signaling and improve neuronal regeneration in a rat SCI model generated using the compression clip method.

Circulating small extracellular vesicles mediate vascular hyperpermeability in diabetes.

Aims/hypothesis: A hallmark chronic complication of type 2 diabetes mellitus is vascular hyperpermeability, which encompasses dysfunction of the cerebrovascular endothelium and the subsequent development of associated cognitive impairment. The present study tested the hypothesis that during type 2 diabetes circulating small extracellular vesicles (sEVs) exhibit phenotypic changes that facilitate pathogenic disruption of the vascular barrier.

Methods: sEVs isolated from the plasma of a mouse model of type 2 diabetes and from diabetic human individuals were characterised for their ability to disrupt the endothelial cell (EC) barrier.

Rejuvenation of the Aging Heart: Molecular Determinants and Applications.

In Canada and worldwide, the elderly population (ie, individuals > 65 years of age) is increasing disproportionately relative to the total population. This is expected to have a substantial impact on the health care system, as increased aged is associated with a greater incidence of chronic noncommunicable diseases. Within the elderly population, cardiovascular disease is a leading cause of death, therefore developing therapies that can prevent or slow disease progression in this group is highly desirable.

Uterine Immunoprivileged Cells Restore Cardiac Function of Male Recipients After Myocardial Infarction.

It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction, being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, we aimed to fill in this gap in knowledge by examining the effects of transplanted uterine cells on infarcted male hearts.

A Novel Conductive Polypyrrole-Chitosan Hydrogel Containing Human Endometrial Mesenchymal Stem Cell-Derived Exosomes Facilitated Sustained Release for Cardiac Repair.

Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)-derived exosomes (hEMSC-Exo) into poly-pyrrole-chitosan (PPY-CHI), to yield an injectable hydrogel that can effectively treat MI.

Combination human umbilical cord perivascular and endothelial colony forming cell therapy for ischemic cardiac injury.

Cell-based therapeutics are promising interventions to repair ischemic cardiac tissue. However, no single cell type has yet been found to be both specialized and versatile enough to heal the heart. The synergistic effects of two regenerative cell types including endothelial colony forming cells (ECFC) and first-trimester human umbilical cord perivascular cells (FTM HUCPVC) with endothelial cell and pericyte properties respectively, on angiogenic and regenerative properties were tested in a rat model of myocardial infarction (MI), in vitro tube formation and Matrigel plug assay.

Heart Failure Impairs Bone Marrow Hematopoietic Stem Cell Function and Responses to Injury.

Background Heart failure (HF) is a clinical syndrome associated with a progressive decline in myocardial function and low-grade systemic inflammation. Chronic inflammation can have lasting effects on the bone marrow (BM) stem cell pool by impacting cell renewal and lineage differentiation. However, how HF affects BM stem/progenitor cells remains largely unexplored.

A Polypyrrole-Polycarbonate Polyurethane Elastomer Alleviates Cardiac Arrhythmias via Improving Bio-Conductivity.

Myocardial fibrosis, resulting from myocardial infarction (MI), significantly alters cardiac electrophysiological properties. As fibrotic scar tissue forms, its resistance to incoming action potentials increases, leading to cardiac arrhythmia, and eventually sudden cardiac death or heart failure. Biomaterials are gaining increasing attention as an approach for addressing post-MI arrhythmias.

Erratum: Young Bone Marrow Sca-1 Cells Rejuvenate the Aged Heart by Promoting Epithelial-to-Mesenchymal Transition: Erratum.

[This corrects the article DOI: 10.7150/thno.22788.

Phenotypic expansion of KCNH1-associated disorders to include isolated epilepsy and its associations with genotypes and molecular sub-regional locations.

Purpose: Genotype-phenotypic correlation of KCNH1 variant remains elusive. This study aimed to expand the phenotypic spectrum of KCNH1 and explore the correlations between epilepsy and molecular sub-regional locations.

Methods: We performed whole-exome sequencing in a cohort of 98 patients with familiar febrile seizure (FS) or epilepsy with unexplained etiologies.

Optimizing human endometrial mesenchymal stem cells for maximal induction of angiogenesis.

Human endometrial mesenchymal stem cells (hEMSCs) have been shown to promote neo-vascularization; however, its angiogenic function lessens with age. To determine the optimal conditions for maximizing hEMSC angiogenic capacity, we examined the effects of serial passaging on hEMSC activity. hEMSCs were cultured from passages (P) 3, 6, 9, and 12, and analyzed for proliferation, migration, differentiation and senescence, as well as their capacity to induce angiogenesis.

Epicardial delivery of a conductive membrane synchronizes conduction to reduce atrial fibrillation.

Conductive polymers have been investigated as a medium for the transmission of electrical signals in biological tissues, but their capacity to rewire cardiac tissue has not been evaluated. Myocardial tissue is unique in being able to generate an electrical potential at a fixed rate; this potential spreads rapidly among cells to trigger muscle contractions. Tissue injuries result in myocardial fibrosis and subsequent non-uniform conductivity, leading to arrhythmia.

Uterus: A Unique Stem Cell Reservoir Able to Support Cardiac Repair via Crosstalk among Uterus, Heart, and Bone Marrow.

Clinical evidence suggests that the prevalence of cardiac disease is lower in premenopausal women compared to postmenopausal women and men. Although multiple factors contribute to this difference, uterine stem cells may be a major factor, as a high abundance of these cells are present in the uterus. Uterine-derived stem cells have been reported in several studies as being able to contribute to cardiac neovascularization after injury.

Compatibility and function of human induced pluripotent stem cell derived cardiomyocytes on an electrospun nanofibrous scaffold, generated from an ionomeric polyurethane composite.

Synthetic scaffolds are needed for generating organized neo-myocardium constructs to promote functional tissue repair. This study investigated the biocompatibility of an elastomeric electrospun degradable polar/hydrophobic/ionic polyurethane (D-PHI) composite scaffold with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The composite material was electrospun to generate scaffolds, with nanofibres oriented in aligned or random directions.

Toward Hierarchical Assembly of Aligned Cell Sheets into a Conical Cardiac Ventricle Using Microfabricated Elastomers.

Despite current efforts in organ-on-chip engineering to construct miniature cardiac models, they often lack some physiological aspects of the heart, including fiber orientation. This motivates the development of bioartificial left ventricle models that mimic the myofiber orientation of the native ventricle. Herein, an approach relying on microfabricated elastomers that enables hierarchical assembly of 2D aligned cell sheets into a functional conical cardiac ventricle is described.

Stroke-Induced Neurological Dysfunction in Aged Mice Is Attenuated by Preconditioning with Young Sca-1+ Stem Cells.

Aims: To date, stroke remains one of the leading causes of death and disability worldwide. Nearly three-quarters of all strokes occur in the elderly (>65 years old), and a vast majority of these individuals develop debilitating cognitive impairments that can later progress into dementia. Currently, there are no therapies capable of reversing the cognitive complications which arise following a stroke.

MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes.

Background: Type 2 diabetes (T2D) is associated with coronary microvascular dysfunction, which is thought to contribute to compromised diastolic function, ultimately culminating in heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms remain incompletely understood, and no early diagnostics are available. We sought to gain insight into biomarkers and potential mechanisms of microvascular dysfunction in obese mouse (db/db) and lean rat (Goto-Kakizaki) pre-clinical models of T2D-associated diastolic dysfunction.

Bio-Conductive Polymers for Treating Myocardial Conductive Defects: Long-Term Efficacy Study.

Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), is able to resynchronize myocardial contractions in vivo.

Aging impairs human bone marrow function and cardiac repair following myocardial infarction in a humanized chimeric mouse.

Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, less is known about how aging affects human BM cells and their ability to regulate repair processes.