Hydrostatic pressure under hypoxia facilitates fabrication of tissue-engineered vascular grafts derived from human vascular smooth muscle cells in vitro.

Biologically compatible vascular grafts are urgently required. The scaffoldless multi-layered vascular wall is considered to offer theoretical advantages, such as facilitating cells to form cell-cell and cell-matrix junctions and natural extracellular matrix networks. Simple methods are desired for fabricating physiological scaffoldless tissue-engineered vascular grafts. Here, we showed that periodic hydrostatic pressurization under hypoxia (HP/HYP) facilitated the fabrication of multi-layered tunica media entirely from human vascular smooth muscle cells. Compared with normoxic atmospheric pressure, HP/HYP increased expression of N-myc downstream-regulated 1 (NDRG1) and the collagen-cross-linking enzyme lysyl oxidase in human umbilical artery smooth muscle cells. HP/HYP increased N-cadherin-mediated cell-cell adhesion via NDRG1, cell-matrix interaction (i.e., clustering of integrin α5ß1 and fibronectin), and collagen fibrils. We then fabricated vascular grafts using HP/HYP during repeated cell seeding and obtained 10-layered smooth muscle grafts with tensile rupture strength of 0.218-0.396 MPa within 5 weeks. Implanted grafts into the rat aorta were endothelialized after 1 week and patent after 5 months, at which time most implanted cells had been replaced by recipient-derived cells. These results suggest that HP/HYP enables fabrication of scaffoldless human vascular mimetics that have a spatial arrangement of cells and matrices, providing potential clinical applications for cardiovascular diseases. STATEMENT OF SIGNIFICANCE: Tissue-engineered vascular grafts (TEVGs) are theoretically more biocompatible than prosthetic materials in terms of mechanical properties and recipient cell-mediated tissue reconstruction. Although some promising results have been shown, TEVG fabrication processes are complex, and the ideal method is still desired. We focused on the environment in which the vessels develop in utero and found that mechanical loading combined with hypoxia facilitated formation of cell-cell and cell-matrix junctions and natural extracellular matrix networks in vitro, which resulted in the fabrication of multi-layered tunica media entirely from human umbilical artery smooth muscle cells. These scaffoldless TEVGs, produced using a simple process, were implantable and have potential clinical applications for cardiovascular diseases.

Transcriptome Analysis Reveals Differential Gene Expression between the Closing Ductus Arteriosus and the Patent Ductus Arteriosus in Humans.

The ductus arteriosus (DA) immediately starts closing after birth. This dynamic process involves DA-specific properties, including highly differentiated smooth muscle, sparse elastic fibers, and intimal thickening (IT). Although several studies have demonstrated DA-specific gene expressions using animal tissues and human fetuses, the transcriptional profiles of the closing DA and the patent DA remain largely unknown. We performed transcriptome analysis using four human DA samples. The three closing DA samples exhibited typical DA morphology, but the patent DA exhibited aorta-like elastic lamellae and poorly formed IT. A cluster analysis revealed that samples were clearly divided into two major clusters, the closing DA and patent DA clusters, and showed distinct gene expression profiles in IT and the tunica media of the closing DA samples. Cardiac neural crest-related genes such as JAG1 were highly expressed in the tunica media and IT of the closing DA samples compared to the patent DA sample. Abundant protein expressions of jagged 1 and the differentiated smooth muscle marker calponin were observed in the closing DA samples but not in the patent DA sample. Second heart field-related genes such as ISL1 were enriched in the patent DA sample. These data indicate that the patent DA may have different cell lineages compared to the closing DA.

Perinatal outcomes of recurrent placental abruption.

INTRODUCTION: The purpose of this study was to classify patients with placental abruption (PA) into those with a history of PA (recurrence group) and those without a history (first-occurrence group), and compare the two groups to investigate whether perinatal outcomes differ between first-time PA and recurrent PA. MATERIALS AND METHODS: Subjects include 6475 patients diagnosed with PA from the Pregnancy Birth Registry System of the Japan Society of Obstetrics and Gynecology. Patients were classified into recurrence group and first-occurrence group. Perinatal outcomes were compared between 141 patients in the recurrence group and 705 patients in the first-occurrence group with 1:5 propensity score matching, adjusting for maternal age, history of smoking, pregnancy-induced hypertension, and premature rupture of membranes as covariates. RESULTS: There were no cases of maternal mortality in either groups, and the perinatal mortality rate did not exhibit a significant difference. Gestational age at delivery was significantly earlier in the recurrence group than in the first-occurrence group (35.3 vs 37.9 weeks, p < .001). The rate of preterm delivery at less than both 32 and 37 weeks of gestation was significantly higher in the recurrence group. The rate of UmApH < 7.1 and 5 min Apgar score < 7 were significantly higher in the recurrence group (21 vs 13%, p = .020, 20% vs 10%, p = .003, respectively). CONCLUSIONS: The results suggest that recurrent PA occurs at an earlier gestational age and follows a more severe course than the first occurrence of PA.

N1 component reflects difference of terminal chords in three-chord sequences.

We understand from experience that musical contexts are formed when chords are combined according to the rules of harmony. In this study, the N1 component of the auditory-evoked potential was measured using comparable three-chord sequences; these sequences were constructed as a consecutive task (cf. C-C-C vs. Cm-Cm-Cm; control) and a cadence task (cf. C-G-C vs. C-G-Cm). In the cadence task, compared with cadences ending with a major chord (anticipated chord), those ending with a minor chord (unanticipated chord) showed a significantly larger amplitude of N1 waves. These components of auditory-evoked potentials reflect the effect of chord progression in musical perception and suggest that the musical context is recognized at least 100 ms after a chord is played.

Prognostic value of brain perfusion single-photon emission computed tomography (SPECT) for language recovery in patients with aphasia.

AIM: To determine the prognostic value of brain perfusion single-photon emission computed tomography (SPECT) in patients with aphasia after a stroke. METHODS: Brain perfusion SPECT with 99mTc-ethyl cysteinate dimer (99mTc-ECD) was used in 16 right-handed patients with aphasia after a left-sided cerebrovascular accident (CVA) in the early chronic period after the onset of CVA. The region of interest (ROI) method was used to calculate the relative regional cerebral blood flow (rCBF) in each cerebral lobe, the thalamus, the putamen and the cerebellum as ratios to the count in the left cerebellar hemisphere. The Standard Language Test of Aphasia (SLTA) was performed twice, once at the same time as SPECT, a mean of 2.3 months after CVA onset (early SLTA), and again a mean of 17.0 months after CVA onset (late SLTA). In addition to the overall language function score, scores for taking dictation (Dictation), oral reading (Speaking) and comprehension (Comprehension) were calculated, and the correlations with each of the rCBF values were evaluated. RESULTS: Left temporal CBF correlated with the late Dictation score; bilateral frontal, bilateral temporal and right parietal CBF correlated with the late Speaking score; and right frontal, left temporal and left occipital CBF correlated with the late Comprehension score. CONCLUSION: Brain perfusion SPECT in the early chronic stage was shown to be useful for predicting recovery from aphasia, recovery of oral reading, ability to take dictation and comprehension.

Auditory lexical-semantic processing impairments in aphasic patients reflected in event-related potentials (N400).

OBJECTIVE: Event-related potentials (ERPs) and response latencies were recorded from aphasic subjects with auditory language processing impairments and age-matched normal controls, while performing a lexical-semantic evaluation task, aiming at clarifying whether ERPs could be a reliable measure for indicating language impairments in aphasic patients. METHODS: The stimuli were 50 pairs of spoken words (prime word-target word): 25 pairs, which were semantically and/or associatively related to each other, and 25 pairs which were not. The subjects pressed a switch in response to the presentation of target words semantically related to the prime words. The ERP component analyzed in this study was N400. RESULTS: With the performances, the response latencies were longer in the aphasic subjects than in the normal controls. With the ERPs, onset latencies of N400 were shifted behind in the aphasic patients compared to the normal controls. For the aphasic patients, there were correlations between the size of N400 and performances in auditory comprehension evaluated in the aphasia test. CONCLUSION: The conclusions drawn from the results are that not only response latencies in the lexical-semantic judgement task, but also N400 effects, may be a reliable clinical measure of the severity of even mild lexical-semantic impairments in aphasic patients.