Children's Hospital Medical Center

Disclosed are methods of treating hemorrhagic shock, for example hemorrhagic shock associated with traumatic injury, gastrointestinal bleeding, spontaneous hemorrhage due to hematologic disorders, uterine hemorrhage, and combinations thereof, in an individual in need thereof. The methods may comprise administering a humanin protein or an analog thereof, for example Humanin G, to the individual.

Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Disclosed herein are methods for treating an individual having, or at risk of having, pulmonary fibrosis, wherein volasertib, a salt thereof, or hydrate thereof, is administered to the individual in need thereof. In one aspect, the pulmonary fibrosis may be idiopathic pulmonary fibrosis. The volasertib may be administered in an amount and for a duration of time effective to achieve one or more outcomes selected from decreased invasiveness of pulmonary fibroblasts, increased clearance of myofibroblasts, decreased migration of pulmonary fibroblasts, decreased pulmonary fibroblast proliferation, decreased cell adhesion of pulmonary fibroblasts, decreased myofibroblast activation, decreased extracellular matrix (ECM) accumulation or production, and improved lung function.

The instant disclosure relates to methods for assessing pulmonary fibrosis disorder disease status in an individual in need thereof. One aspect of the disclosed methods may comprise: detecting a level of one or more biomarkers in a biological sample obtained from an individual, comparing the level of the one or more biomarkers to that of a control value corresponding to the one or more biomarkers, characterizing the disease status in the individual based on the level of the one or more biomarkers as compared to that of a relevant control value; and administering a treatment to said individual based on the assessment of the one or more biomarker levels.

Administering a pulmonary surfactant and a corticosteroid in a low dose is effective for the prophylaxis of bronchopulmonary dysplasia (BPD) in preterm neonates.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

Production and maintenance of hematopoietic stem cells in in vitro culture systems has proven to be elusive. Disclosed herein are hematopoietic stem cell compositions that originate from organoids such as liver organoids. These organoids also comprise a rare type of immune cell that is not yet fully elucidated due to the difficulty in isolating said immune cell from biological samples. Also disclosed herein are methods of producing said hematopoietic stem cells and immune cells from organoids, as well as methods of expanding hematopoietic stem cells from other sources using these organoids.

Disclosed herein are methods for enhancing an immune response in an individual in need thereof. The methods, in certain aspects, may comprise administering bacterial aldehyde dehydrogenase, a bacteria that produces aldehyde dehydrogenase, or combinations thereof to an individual. Further disclosed are compositions, such as nutritional compositions, which may comprise bacterial aldehyde dehydrogenase, a bacteria that produces aldehyde dehydrogenase, or combinations thereof.

Some embodiments of the disclosure include inventive compounds (e.g., compounds of Formula (I)) and compositions (e.g., pharmaceutical compositions) which inhibit IRAK and/or FLT3 and which can be used for treating, for example, certain diseases. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as hematopoietic cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), etc.), Additional embodiments provide disease treatment using combinations of the inventive IRAK and/or FLT3 inhibiting compounds with other therapies, such as cancer therapies.

Disclosed herein are methods of generating intestinal organoids (IO) with immune cells (iIO) and methods of making an iIO with activated immune cells. IO compositions including immune cells, optionally including activated immune cells, (iIO) are also disclosed herein. Also disclosed are iIO models of disease states. Further disclosed are methods of treatment including transplanting iIO into an organism, as well as methods of screening a compound for activity using an iIO, for example an iIO model of a disease state.