Bruno, D. | bioRxiv Science

bioRxiv2020

Human saphenous vein provides a unique source of anti-calcific pericytes for prosthetic cardiac valve engineering

AimsTissue engineering seeks to improve the longevity of prosthetic heart valves, but the cell source of choice has yet to be determined. This study aimed to establish a mechanistic rationale supporting the suitability of human adventitial pericytes (APCs). Methods and ResultsAntigenically APCs were immunomagnetically sorted from saphenous vein leftovers of patients undergoing coronary artery surgery and antigenically characterized for purity. Unlike bone marrow-derived mesenchymal stromal cells (BM-MSCs), APCs were resistant to osteochondrogenic induction by high phosphate (HP), as assessed by cytochemistry and expression of osteogenic markers. MiR-132 is natively expressed by APCs, with copy numbers being enhanced by HP stimulation. In silico bioinformatic analysis, followed by luciferase assays in HEK293 cells and miR-132 titration using agomiR and antagomiR in APCs, demonstrated that several osteochondrogenic genes were negatively regulated by miR-132. Among these, the glycolytic marker GLUT1 was downregulated in HP-stimulated APCs. In contrast to BM-APCs, APCs showed no increase in glycolysis under HP. Interestingly, incubation with APC-derived conditioned medium conferred swine cardiac valves with resistance to osteogenic transformation by HP; whereas, conditioned media from miR-132-knocked-down APCs failed to prevent the expression of these markers. Finally, we demonstrated the feasibility of using APCs to engineer bovine pericardium patches. APCs proliferate in the patch and secrete factors able to attract aortic endothelial cells under HP. ConclusionsHuman APCs are resistant to calcification compared with BM-MSCs and convey the anti-calcific phenotype to heart valves through miR-132. These findings may open new important avenues for prosthetic valve cellularization.

cell biology↗

bioRxiv2020

Proper names from story recall are associated with beta-amyloid in cognitively unimpaired adults at risk for Alzheimer's disease

Due to advances in the early detection of Alzheimers disease (AD) biomarkers including beta-amyloid (A{beta}), neuropsychological measures that are sensitive to concurrent, subtle changes in cognition are critically needed. Story recall tasks have shown sensitivity to early memory declines in persons with Mild Cognitive Impairment and early stage dementia, as well as in persons with autosomal dominantly inherited AD up to 10 years prior to a dementia diagnosis. However, the evidence is inconclusive regarding relationships between evidence of A{beta} and story recall measures. Because story recall tasks require the encoding and delayed retrieval of several lexical-semantic categories, such as proper names, verbs, and numerical expressions, and because lexical categories have been shown to be differentially impaired in persons with MCI, we focused on item-level analyses of lexical-semantic retrieval from a quintessential story recall task, Logical Memory from the Wechsler Memory Scale. Our objective was to investigate whether delayed recall of lexical categories (proper names, verbs and/or numerical expressions), as well as the traditional total score measure, was associated with "preclinical AD," or cognitively unimpaired adults with positive A{beta} deposition on positron emission tomography (PET) neuroimaging using Pittsburgh Compound B. We developed an item-level scoring system, in which we parsed items into lexical categories and examined the immediate and delayed recall of these lexical categories from 217 cognitively unimpaired participants from the Wisconsin Registry for Alzheimers Prevention. We performed binary logistic regression models with story recall score as predictor and A{beta} status (positive/negative) as the outcome. Using baseline Logical Memory data, proper names from delayed story recall were significantly associated with A{beta} status, such that participants who recalled more proper names were less likely to be classified as PiB(+) (odds ratio = .58, p=.01). None of the other story recall variables, including total score, were associated with PiB status. Secondary analyses determined that immediate recall of proper names was not significantly associated with A{beta}, suggesting a retrieval deficit rather than that of encoding. The present findings suggest that lexical semantic retrieval measures from existing story recall tasks may be sensitive to A{beta} deposition, and may provide added utility to a widely-used, long-standing neuropsychological test for early detection of cognitive decline on the AD continuum.

neuroscience↗