Neonatal engraftment by oligodendrocyte progenitor cells (OPCs) permits the myelination of congenitally dysmyelinated brain. To establish a potential autologous source of these cells, we developed a strategy by which to differentiate human induced pluripotential stem cells (hiPSCs) into OPCs. From 3 hiPSC lines, as well as from human embryonic stem cells (hESCs), we generated highly enriched OLIG2+/PDGFRα+/NKX2.2+/SOX10+ hOPCs, which could be further purified using fluorescence-activated cell sorting. hiPSC OPCs efficiently differentiated into both myelinogenic oligodendrocytes and astrocytes, in vitro and in vivo. Neonatally engrafted hiPSC OPCs robustly myelinated the brains of myelin-deficient shiverer mice, and substantially increased the survival of these mice. The speed and efficiency of myelination by hiPSC OPCs was higher than that previously observed using fetal tissue-derived OPCs, and no tumors from these grafts were noted as long as 9 months after transplant. These results suggest the utility of hiPSC-derived OPCs in treating disorders of myelin loss.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show that African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days after exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin-6 pathways in bronchoalveolar lavage samples and repression of natural killer cell-and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures.

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BackgroundDogs are a unique model for examining the effects of exercise on vitamin D status because of their lack of vitamin D synthesis by UV exposure. In addition, the inflammatory response may be associated with hypovitaminosis D.ObjectivesTo investigate the effects of several days of endurance exercise on plasma vitamin D (25‐(OH)D3, 24,25‐(OH)D3 and 1,25(OH)D3) and serum C‐reactive protein (CRP) concentrations in stage‐stop racing sled dogs.Animals12 racing sled dogs and 8 control dogs.MethodsBlood was collected before the race and immediately after racing on days 2 and 8. Plasma vitamin D metabolites and serum CRP concentrations were measured.ResultsRacing dogs showed a significant increase in 25(OH)D3 on day 2 (P = .027) and day 8 of the race (P < .001), whereas no increases were observed in control dogs. The plasma concentration of 24,25(OH)D3 showed a significant increase by day 8 (P < .001). There were no significant changes in 1,25(OH) D3 concentrations across all time points and groups. Racing dogs had significantly increased CRP concentrations by day 2 (39.3 ± 30.1 μg/mL; P < .001).Conclusions and Clinical ImportanceIncreases in vitamin D metabolites as well as increases in CRP concentrations were observed in racing sled dogs. This finding was contrary to the hypothesis that decreases in vitamin D status in athletes may be related to the acute phase inflammatory response during exercise. In addition, the increased 24,25(OH)D3 concentrations compared to what is observed in other species suggests metabolic variations in dogs that lead to enhanced disposal of vitamin D.