Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.

Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.

Propagation Mapping Wave Collision Correlates to the Site of Successful Ablation During Voltage Mapping in Atrioventricular Nodal Reentry Tachycardia.

Voltage mapping has been used previously for slow-pathway localization for atrioventricular nodal reentrant tachycardia (AVNRT) ablation. However, propagation mapping may be a technique to further improve the localization of the slow pathway. This retrospective study aimed to evaluate the relationship of the propagation map to both the voltage mapping and successful site of ablation in patients who underwent ablation for AVNRT. All patients ≤20 years of age who underwent voltage mapping for AVNRT were included in this study. Patients were excluded if they had congenital heart disease or inadequate voltage point density within the triangle of Koch (TK). During the study, a propagation map was evaluated from the prior voltage map, marking a "wave collision" at the site of atrial wave convergence. Patient and procedural information, the location of the wave collision, the site of successful ablation, and the appearance of the voltage map were evaluated. Ultimately, 39 patients aged from four years of age to 20 years of age were evaluated. Success was achieved in 100% of patients, with a recurrence rate of 2.8% and no long-term complications observed. The average procedure time was 127 min. Follow-up length averaged seven months post operation. Low-voltage areas, and a wave collision, were present in all patients. This wave collision was typically located within the TK. The median number of ablations required for successful outcome was two. The successful ablation lesion was typically located over a low-voltage area within 4 mm of the wave collision within the TK. In conclusion, we found in this retrospective evaluation that propagation mapping resulted in a wave collision within the TK, and that the successful ablation site in the majority of patients was near a low-voltage area within 4 mm, typically superiorly, to the wave collision within the TK.