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Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric neural stem cells (ENSCs) to rescue the enteric nervous system (ENS) in a model of colonic aganglionosis. ENSCs are isolated from a segment of small intestine from Wnt1::Cre;R26iDTR mice in which focal colonic aganglionosis is simultaneously created by diphtheria toxin injection. Autologous ENSCs are isolated, expanded, labeled with lentiviral-GFP, and transplanted into the aganglionic segment in vivo. ENSCs differentiate into neurons and glia, cluster to form neo-ganglia, and restore colonic contractile activity as shown by electrical field stimulation and optogenetics. Using a non-lethal model of colonic aganglionosis, our results demonstrate the potential of autologous ENSC therapy to improve functional outcomes in neurointestinal disease, laying the groundwork for clinical application of this regenerative cell-based approach.Neurointestinal diseases cause significant morbidity and effective treatments are lacking. Here, authors perform autologous cell transplantation of enteric neural stem cells in a mouse model of colonic aganglionosis and report restoration of colonic contractile activity. [ABSTRACT FROM AUTHOR]

In mammals, neural crest cells populate the gut and form the enteric nervous system (ENS) early in embryogenesis. Although the basic ENS structure is highly conserved across species, we show important differences between mice and humans relating to the prenatal and postnatal development of mucosal enteric glial cells (mEGC), which are essential ENS components. We confirm previous work showing that in the mouse mEGCs are absent at birth, and that their appearance and homeostasis depends on postnatal colonization by microbiota. In humans, by contrast, a network of glial cells is already present in the fetal gut. Moreover, in xenografts of human fetal gut maintained for months in immuno-compromised mice, mEGCs persist following treatment with antibiotics that lead to the disappearance of mEGCs from the gut of the murine host. Single cell RNAseq indicates that human and mouse mEGCs differ not only in their developmental dynamics, but also in their patterns of gene expression. [ABSTRACT FROM AUTHOR]

Dual-task gait performance is impaired in older adults with mild cognitive impairment, but the brain substrates associated with dual-task gait performance are not well-established. The relationship between gray matter and gait speed under single-task and dual-task conditions (walking while counting backward) was examined in 560 seniors with mild cognitive impairment (non-amnestic mild cognitive impairment: n = 270; mean age = 72.4 yrs., 63.6 % women; amnestic mild cognitive impairment: n = 290; mean age = 73.4 yrs., 45.4 % women). Multivariate covariance-based analyses of magnetic resonance imaging data, adjusted for potential confounders including single-task gait speed, were performed to identify gray matter patterns associated with dual-task gait speed. There were no differences in gait speed or cognitive performance during dual-task gait between individuals with non-amnestic mild cognitive impairment and amnestic mild cognitive impairment. Overall, increased dual-task gait speed was associated with a gray matter pattern of increased volume in medial frontal gyrus, superior frontal gyrus, anterior cingulate, cingulate, precuneus, fusiform gyrus, middle occipital gyrus, inferior temporal gyrus and middle temporal gyrus. The relationship between dual-task gait speed and brain substrates also differed by mild cognitive impairment subtype. Our study revealed a pattern of gray matter regions associated with dual-task performance. Although dual-task gait performance was similar in amnestic and non-amnestic mild cognitive impairment, the gray matter patterns associated with dual-task gait performance differed by mild cognitive impairment subtype. These findings suggest that the brain substrates supporting dual-task gait performance in amnestic and non-amnestic subtypes are different, and consequently may respond differently to interventions, or require different interventions. [ABSTRACT FROM AUTHOR]

The linkage between gait and cognition has been shown in cases of white matter lesion (WML) that affect gait in older adults. Dual-task walking is believed to be cognitively demanding and to alter trunk movement, and gait impairment in people with mild cognitive impairment (MCI) is highlighted under this condition. However, the association between dual-task walking and structural changes in the brain, particularly with WML, in people with MCI is still unclear. The aim of this study was to examine the association between trunk stability during dual-task walking and WML in 560 older adults with MCI. We measured magnetic resonance imaging (MRI) and gait variables. Gait variables included harmonic ratio in vertical, mediolateral, and anteroposterior directions, analyzed using a tri-axial accelerometer attached to the lower trunk. Walking conditions were normal walking and dual-task walking (counting backwards while walking) conditions. Demographical data and brain atrophy were measured as covariates. Subjects were classified into non-severe WML (n = 451, mean age = 73.2 years) and severe WML (n = 109, mean age = 75.9 years) groups. Linear mixed-effects model analysis controlled for covariates showed dual-task-related changes in all harmonic ratios associated with WML (p < 0.05). Even after adjustment for executive function, harmonic ratio in the mediolateral direction was significantly associated with WML (p < 0.05). Our findings revealed that WMLs were associated with trunk stability in dual-task walking. Further studies are required to investigate the neural basis for deficits in gait ability among MCI subjects. [ABSTRACT FROM AUTHOR]

Stem cell therapy offers the potential of rebuilding the enteric nervous system (ENS) in the aganglionic bowel of patients with Hirschsprung's disease. P0-Cre/Floxed-EGFP mice in which neural crest-derived cells express EGFP were used to obtain ENS stem/progenitor cells. ENS stem/progenitor cells were transplanted into the bowel of Ret mouse, an animal model of Hirschsprung's disease. Immunohistochemical analysis was performed to determine whether grafted cells gave rise to neurons in the recipient bowel. EGFP expressing neural crest-derived cells accounted for 7.01 ± 2.52 % of total cells of gastrointestinal tract. ENS stem/progenitor cells were isolated using flow cytometry and expanded as neurosphere-like bodies (NLBs) in a serum-free culture condition. Some cells in NLBs expressed neural crest markers, p75 and Sox10 and neural stem/progenitor cells markers, Nestin and Musashi1. Multipotency of isolated ENS stem/progenitor cells was determined as they differentiated into neurons, glial cells, and myofibloblasts in culture. When co-cultured with explants of hindgut of Ret mice, ENS stem/progenitor cells migrated into the aganglionic bowel and gave rise to neurons. ENS stem/progenitor cells used in this study appear to be clinically relevant donor cells in cell therapy to treat Hirschsprung's disease capable of colonizing the affected bowel and giving rise to neurons. [ABSTRACT FROM AUTHOR]

Portal venous stenosis is relatively a rare complication after liver transplantation in children and it sometimes leads to life threatening event due to gastrointestinal bleeding or graft failure. Recently, balloon dilatation has been widely accepted as a treatment of choice for the management of portal venous stenosis. The purpose of this study was to evaluate the feasibility of transileocolic venous balloon dilatation for the management of primary and recurrent portal venous stenosis after living donor liver transplantation (LDLT) in children. The records of 57 pediatric liver transplants were retrospectively reviewed. Nine patients (15.8%) with portal venous stenosis were identified. Seven symptomatic children with portal venous stenosis underwent balloon dilatation. Two approaches were employed for balloon dilatation; the transileocolic venous approach and the percutaneous transhepatic approach. In patients with recurrent stenosis, careful follow-up was carried out while they were asymptomatic. Twelve balloon dilatations were performed in seven children with primary or recurrent portal venous stenoses. The initial technical success rate was 91.7% (11/12), while 6 out of 12 (50.0%) procedures resulted in recurrent stenosis. Five out of six recurrent stenoses required repeated balloon dilatation. The clinical success rate of balloon dilatation in our study was 85.7% (6/7). Other than recurrent stenosis, two procedure-related complications occurred. In conclusion, transileocolic venous balloon dilatation was a safe and effective procedure for portal venous stenosis after LDLT in children. [ABSTRACT FROM AUTHOR]

Antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes for Chang cells coated with antibody to liver specific membrane lipoprotein was studied in patients with chronic active liver diseases (CALD) to investigate the pathogenesis of liver cell injury. Of 20 CALD patients, a reduced ADCC was found in 5 cases, whereas an increased ADCC was noted in 8 cases. The remaining 7 cases showed a normal ADCC. There was a significant correlation (p<0.01) between a decreased ADCC and an increased level of immune complexes in the sera of CALD patients when aI-Clq binding test was used. When sera from ADCC patients, which had a high level of circulating immune complexes, or aggregated human IgG was added, ADCC of normal lymphocytes was significantly inhibited (p<0.01) compared with that of lymphocytes alone. These results suggest that circulating immune complexes play a role on the pathogenesis of liver damage in CALD. [ABSTRACT FROM AUTHOR]