Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Objective: To identify risk alleles relevant to the causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: A genome-wide association study and subsequent replication study were conducted in a total cohort of 1,986 cases of AAV (patients with granulomatosis with polyangiitis [Wegener's] [GPA] or microscopic polyangiitis [MPA]) and 4,723 healthy controls. Meta-analysis of these data sets and functional annotation of identified risk loci were performed, and candidate disease variants with unknown functional effects were investigated for their impact on gene expression and/or protein function.

Expression of the vasoactive proteins AT1, AT2, and ANP by pregnancy-induced mouse uterine natural killer cells.

Angiotensin II receptor type 1 (AT1) activation leads to vasoconstriction and type 2 receptor (AT2) leads to vasodilation. Atrial natriuretic peptide (ANP) antagonizes the effects of AT1. In human and murine pregnancies, uterine natural killer (uNK) cells closely associate with decidual blood vessels.

What's new in cardiac cell therapy? Allogeneic bone marrow stromal cells as "universal donor cells".

Cardiac cell therapies offer distinct and exciting advantages over current treatments to prevent postinfarction heart failure because they can reverse ventricular remodeling and improve function, but only if the implanted stem cells contribute biological functions and achieve prolonged engraftment within the hostile environment of the damaged heart. Unfortunately, function is diminished in autologous stem cells isolated from older patients and those with comorbidities, and so clinical trials testing the implantation of healthy, allogeneic bone marrow-derived stromal cells (MSCs) isolated from young donors are currently underway. MSCs are unique because, in addition to exerting paracrine effects that restore blood flow and recruit endogenous stem cells to the infarct, they exhibit immune-modulating properties in culture that-if retained after allogeneic implantation-imply the cells may escape immune recognition within the heart.

Co-culture with cardiomyocytes enhanced the myogenic conversion of mesenchymal stromal cells in a dose-dependent manner.

To increase the accessibility of myogenic cells for cell therapy in the infarcted heart, we identified conditions to improve the reproducible conversion of bone marrow mesenchymal stromal cells (BMSCs) into myogenic cells. Such cells may permit functional regeneration following a myocardial infarction. BMSCs derived from green fluorescent protein (GFP) transgenic rats were co-cultured with neonatal rat cardiomyocytes (1:1, 1:10, 1:20, and 1:40 ratios) for 7 days.

Aging impairs the angiogenic response to ischemic injury and the activity of implanted cells: combined consequences for cell therapy in older recipients.

Objective: Cell therapy has received much attention for its potential to regenerate ischemic organs, but initial clinical trials in aged patients did not replicate the dramatic benefits recorded in preclinical studies with young animals. This study was designed to improve our understanding of age-related changes in the response to ischemic injury and the regenerative capacity of implanted cells in the context of cell therapy for older recipients.

Methods And Results: Restoration of regional perfusion after hind limb femoral artery ligation was impaired (P < .

Intravenously administered bone marrow cells migrate to damaged brain tissue and improve neural function in ischemic rats.

Accumulated evidence suggests that bone marrow stromal cells (BMSCs) are capable of regenerating damaged tissue. This study evaluated whether intravenously (noninvasively) administered, GFP-labeled BMSCs would migrate into damaged brain tissue and improve neurological function after a stroke. Wistar rats were subjected to middle cerebral artery occlusion and reperfusion.

Intravenously Administered Bone Marrow Cells Migrate to Damaged Brain Tissue and Improve Neural Function in Ischemic Rats.

Accumulated evidence suggests that bone marrow stromal cells (BMSCs) are capable of regenerating damaged tissue. This study evaluated whether intravenously (noninvasively) administered, GFP-labeled BMSCs would migrate into damaged brain tissue and improve neurological function after a stroke. Wistar rats were subjected to middle cerebral artery occlusion and reperfusion.