Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.

Regenerating human skeletal muscle forms an emerging niche in vivo to support PAX7 cells.

Skeletal muscle stem and progenitor cells including those derived from human pluripotent stem cells (hPSCs) offer an avenue towards personalized therapies and readily fuse to form human-mouse myofibres in vivo. However, skeletal muscle progenitor cells (SMPCs) inefficiently colonize chimeric stem cell niches and instead associate with human myofibres resembling foetal niches. We hypothesized competition with mouse satellite cells (SCs) prevented SMPC engraftment into the SC niche and thus generated an SC ablation mouse compatible with human engraftment. Single-nucleus RNA sequencing of SC-ablated mice identified the absence of a transient myofibre subtype during regeneration expressing Actc1. Similarly, ACTC1+ human myofibres supporting PAX7+ SMPCs increased in SC-ablated mice, and after re-injury we found SMPCs could now repopulate into chimeric niches. To demonstrate ACTC1+ myofibres are essential to supporting PAX7 SMPCs, we generated caspase-inducible ACTC1 depletion human pluripotent stem cells, and upon SMPC engraftment we found a 90% reduction in ACTC1+ myofibres and a 100-fold decrease in PAX7 cell numbers compared with non-induced controls. We used spatial RNA sequencing to identify key factors driving emerging human niche formation between ACTC1+ myofibres and PAX7+ SMPCs in vivo. This revealed that transient regenerating human myofibres are essential for emerging niche formation in vivo to support PAX7 SMPCs.

Alveolar bone loss and mineralization in the pig with experimental periodontal disease.

OBJECTIVE: To address how experimental periodontal disease affects alveolar bone mass and mineral apposition in a young pig model. MATERIALS AND METHODS: Seven three-month-old pigs were periodically inoculated with 4 types of periodontal bacteria, along with a ligature around the last maxillary deciduous molar for 8 weeks to induce periodontal disease (PG). Eight same-aged pigs served as the control (CG). Segmentations of 3D cone-beam CT images were performed to quantify volumes of the total alveolar bone, alveolar ridge, and all roots of the target molar. Calcein and alizarin were administered for labeling mineral apposition before euthanasia. The harvested molar blocks were sectioned and examined under epifluorescence. The inter-label distance between the two vital markers at regional bone surfaces were measured and mineral apposition rate (MAR) was calculated. RESULTS: A significant reduction of total alveolar bone volume was seen in PG with the major loss at the alveolar ridge. MAR was significantly higher at the root furcation region than those at both buccal and palatal ridges in CG. Compared with CG, PG animals showed more interrupted labeled bands with significantly lower MAR at the furcation region. MARs were positively associated with both the volumes of total alveolar bone and ridge in CG, but only with the total alveolar bone in PG. CONCLUSIONS: In young growing pigs, mineral apposition is region specific. The experimental periodontal disease not only leads to alveolar bone loss, but also perturbs mineral apposition for new bone formation, thus impairing the homeostasis of alveolar bone remodeling.