Background Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been widely used due to their multipotency, a broad range of sources, painless collection, and compliance with standard amplification. Cell sheet technology is a tissue engineering methodology requiring scaffolds free, and it provides an effective method for cell transplantation. To improve the therapeutic efficacy, we combined hUC-MSCs with cell sheet technology to evaluate the safety and efficacy of hUC-MSC sheets in preclinical studies using appropriate animal models. Methods hUC-MSC sheets were fabricated by hUC-MSCs from a cell bank established by a standard operation process and quality control. Cytokine secretion, immunoregulation, and angiopoiesis were evaluated in vitro. Oncogenicity and cell diffusion assays of hUC-MSC sheets were conducted to verify the safety of hUC-MSCs sheet transplantation in mice. To provide more meaningful animal experimental data for clinical trials, porcine myocardial infarction (MI) models were established by constriction of the left circumflex, and hUC-MSC sheets were transplanted onto the ischemic area of the heart tissue. Cardiac function was evaluated and compared between the experimental and MI groups. Results The in vitro results showed that hUC-MSC sheets could secrete multiple cellular factors, including VEGF, HGF, IL-6, and IL-8. Peripheral blood mononuclear cells had a lower proliferation rate and lower TNF-α secretion when co-cultured with hUC-MSC sheets. TH1 cells had a smaller proportion after activation. In vivo safety results showed that the hUC-MSCs sheet had no oncogenicity and was mainly distributed on the surface of the ischemic myocardial tissue. Echocardiography showed that hUC-MSC sheets effectively improved the left ventricular ejection fraction (LVEF), and the LVEF significantly changed (42.25 ± 1.23% vs. 66.9 ± 1.10%) in the hUC-MSC transplantation group compared with the MI group (42.52 ± 0.65% vs. 39.55 ± 1.97%) at 9 weeks. The infarct ratio of the hUC-MSCs sheet transplantation groups was also significantly reduced (14.2 ± 4.53% vs. 4.00 ± 2.00%) compared with that of the MI group. Conclusion Allogeneic source and cell bank established by the standard operation process and quality control make hUC-MSCs sheet possible to treat MI by off-the-shelf drug with universal quality instead of individualized medical technology.
We aim to explore the link between maternal weekly temperature exposure and CHD in offspring and identify the relative contributions from heat and cold and from moderate and extreme atmospheric temperature. From January 2019 to December 2020, newborns who were diagnosed with CHD by echocardiography in the Network Platform for Congenital Heart Disease (NPCHD) from 11 cities in eastern China were enrolled in the present study. We appraised the exposure lag response relationship between temperature and CHDs in the distributed lag nonlinear model and further probed the pooled estimates by multivariate meta-analysis. We further performed the exposure–response curves in extreme temperature (5 th percentile for cold and 95 th for hot events). We also delve into the cumulative risk ratios (CRRs) of temperature on CHDs in general and subgroups. In this study, 5904 of 983, 523 infants were diagnosed with CHDs. The temperature-CHD combination performed positive significance in two exposure windows, gestational weeks 10–16 and 26–31, and reached the maximum effect in the 28th week. Compared with extreme cold (5 th , 6.14℃), these effects were higher in extreme heat (95 th , 29.26℃). The cumulative exposure–response curve showed a steep nonlinear rise in the hot tail but showed non-significance at low temperatures. In this range, the CRRs of temperature showed an increment to a ceiling of 3.781 (95% CI: 1.460–10.723). The temperature- CHD curves for both sex groups showed a general growth trend. No statistical significance was observed between these two groups ( P = 0.106). The cumulative effect of the temperature related CHD was significant in regions with lower education levels (maximum CRR was 9.282 (3.019–28.535)). A degree centigrade increase in temperature exposure was associated with the increment of CHD risk in the first and second trimesters, especially in extreme heat. Neonates born in lower education regions were more vulnerable to temperature-related CHDs. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-022-24396-5.
Objective: To evaluate the value of radiomics models created based on non-contrast enhanced T1-weighted (T1W) and T2W fat-saturated (T2WFS) images for staging hepatic fibrosis (HF) and grading inflammatory activity. Methods and materials: Data of 280 patients with pathologically confirmed HF and 48 healthy volunteers were included. The participants were divided into the training set and the test set at the proportion of 4:1 by the random seed method. We used the Pyradiomics software to extract radiomics features, and then use the least absolute shrinkage and selection operator to select the optimal subset. Finally, we used the stochastic gradient descent classifier to build the prediction models. DeLong test was used to compare the diagnostic performance of the models. Receiver operating characteristics was used to evaluate the prediction ability of the models. Results: The diagnostic efficiency of the models based on T1W&T2WFS images were the highest (all p < 0.05). When discriminating significant fibrosis (≥ F2), there were significant differences in the area under the receiver operating characteristic curves (AUCs) between the machine learning models based on T1W and T2WFS images (p < 0.05), but there were no significant differences in AUCs between the two models in other groups (all p > 0.05). Conclusion: The radiomics models built on T1W and T2WFS images are effective in assessing HF and inflammatory activity. Advances in knowledge: Based on conventional MR sequences that are readily available in the clinic, namely unenhanced T1W and T2W images. Radiomics can be used for diagnosis and differential diagnosis of liver fibrosis staging and inflammatory activity grading.
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