Systems for the Functional Evaluation of Human Heart Tissues Derived from Pluripotent Stem Cells

Human pluripotent stem cells (hPSCs) are expected to be a promising cell source in regenerative medicine and drug discovery for the treatment of various intractable diseases. An approach for creating a 3-dimensional (3D) structure from hPSCs that mimics human cardiac tissue functions has made it theoretically possible to conduct drug discovery and cardiotoxicity tests by assessing pharmacological responses in human cardiac tissues by a screening system using a compound library. The myocardium functions as a tissue composed of organized vascular networks, supporting stromal cells and cardiac muscle cells. Considering this, the reconstruction of tissue structure by various cells of cardiovascular lineages, such as vascular cells and cardiac muscle cells, is desirable for the ideal conformation of hPSC-derived cardiac tissues. Heart-on-a-chip, an organ-on-a-chip system to evaluate the physiological pump function of 3D cardiac tissues might hold promise in medical researchs such as drug discovery and regenerative medicine. Here, we review various modalities to evaluate the function of human stem cell-derived cardiac tissues and introduce heart-on-a-chip systems that can recapitulate physiological parameters of hPSC-derived cardiac tissues

Both the anaerobic pathway and aerobic desaturation are involved in the synthesis of unsaturated fatty acids in Vibrio sp. strain ABE-1

AbstractVibrio sp. strain ABE-1 is a unique marine bacterium in terms of its ability to synthesize Δ9-trans-hexadecenoic acid and Δ7-cis-tetradecenoic acid (14:1(7c); Okuyama, H., Sasaki, S., Higashi, S. and Murata, N. (1990) J. Bacteriol. 172, 3515-3518). The present study, involving labeling with [1-14C]acetate, demonstrated that 14:1 is synthesized by the anaerobic pathway. When cells of this bacterium were grown in the presence of [1-14C]myristic acid (14:0), this compound was converted to palmitic (16:0) and hexadecenoic (16:1) acids but not to 14:1, under aerobic conditions. These results suggest that the incorporated 14:0 was elongated to 16:0 and then converted to 16:1 by the aerobic desaturation of 16:0. It appears that the anaerobic pathway and aerobic desaturation are both involved in the synthesis of unsaturated fatty acids during aerobic growth of Vibrio sp. strain ABE-1

A novel approach for the endothelialization of xenogeneic decellularized vascular tissues by human cells utilizing surface modification and dynamic culture

Decellularized xenogeneic vascular grafts can be used in revascularization surgeries. We have developed decellularization methods using high hydrostatic pressure (HHP), which preserves the extracellular structure. Here, we attempted ex vivo endothelialization of HHP-decellularized xenogeneic tissues using human endothelial cells (ECs) to prevent clot formation against human blood. Slices of porcine aortic endothelium were decellularized using HHP and coated with gelatin. Human umbilical vein ECs were directly seeded and cultured under dynamic flow or static conditions for 14 days. Dynamic flow cultures tend to demonstrate higher cell coverage. We then coated the tissues with the E8 fragment of human laminin-411 (hL411), which has high affinity for ECs, and found that Dynamic/hL411showed high area coverage, almost reaching 100% (Dynamic/Gelatin vs Dynamic/hL411; 58.7 ± 11.4 vs 97.5 ± 1.9%, P = 0.0017). Immunostaining revealed sufficient endothelial cell coverage as a single cell layer in Dynamic/hL411. A clot formation assay using human whole blood showed low clot formation in Dynamic/hL411, almost similar to that in the negative control, polytetrafluoroethylene. Surface modification of HHP-decellularized xenogeneic endothelial tissues combined with dynamic culture achieved sufficient ex vivo endothelialization along with prevention of clot formation, indicating their potential for clinical use as vascular grafts in the future

Japanese multicenter database of healthy controls for [¹²³I]FP-CIT SPECT

Purpose: The aim of this multicenter trial was to generate a [¹²³I]FP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan. Methods: This study included 510 sets of SPECT data from 256 healthy controls (116 men and 140 women; age range, 30–83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom. Results: The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30–39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70–79 age group. Conclusions: This study provided a large-scale quantitative database of [¹²³I]FP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database