CASE REPORT: A 35-year-old woman delivered a stillborn female fetus at 33 weeks of gestation. No fetal anomaly was detected. Examination of the umbilical cord showed multiple strictures, located 4.5 cm and 20 cm from the placental insertion site. Microscopically, the stricture site showed Wharton's jelly being replaced by fibrosis with presence of vascular thrombosis.
DISCUSSION: Umbilical cord stricture is uncommon and has been described to be associated with intrauterine fetal death and a possibility of recurrent. There is a need to counsel the parents and close fetal surveillance in subsequent pregnancy is advise since the risk of recurrent remains uncertain.
Methods: A conditioned medium of umbilical cord-derived MSCs (UCMSC-CM) was generated by culturing the cells on serum-free αMEM for 24 h. Following this, human GBM T98G cells were treated with UCMSC-CM for 24 h. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was then performed to measure the mRNA expression of survivin, caspase-9, TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DcR1.
Results: mRNA expression of caspase-9 in CM-treated T98G cells increased 1.6-fold (P = 0.017), whereas mRNA expression of survivin increased 3.5-fold (P = 0.002). On the other hand, TRAIL protein expression was upregulated (1.2-fold), whereas mRNA expression was downregulated (0.4-fold), in CM-treated cells. Moreover, there was an increase in the mRNA expression of both DR4 (3.5-fold) and DcR1 (1,368.5-fold) in CM-treated cells.
Conclusion: The UCMSC-CM was able to regulate the expression of molecules involved in GBM cell apoptotic pathways. However, the expression of anti-apoptotic molecules was more upregulated than that of pro-apoptotic molecules.
Results: 11 healthy subjects (LD, n = 5; HD, n = 6; mean age of 55 ± 13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA (705 ± 160 vs. 306 ± 36 pg/mL; p = 0.02) and IL-10 (321 ± 27 vs. 251 ± 28 pg/mL; p = 0.02); and lower levels of proinflammatory marker TNF-α (74 ± 23 vs. 115 ± 15 pg/mL; p = 0.04) compared to LD group.
Conclusion: Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.
METHODS: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student's t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD).
RESULTS: Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD.
CONCLUSIONS: In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.