The present invention is directed to compositions and methods to increase the expression of PD-L1 and/or IDO-1 in a population of cells, the modulated cells expressing increased PD-L1 and/or IDO-1, and methods related to the immunosuppressive effects obtained by cells expressing increased PD-L1 and/or IDO-1.

This document relates to bioengineering and involves bioengineered thymus organoids and related humanized animal models. The thymus organoids and animal models have various commercial and clinical uses, including generating humanized antibodies, making antigen-specific human T cells, inducing transplantation tolerance, rejuvenating thymus functions, and modeling human diseases.

In various embodiments methods of producing a cell population enriched for CLEC9A+ dendritic cells are provided where the methods involve culturing stem cells and/or progenitor cells in a cell culture comprising culture medium, a notch ligand, stem cell factor (SCF), FLT3 ligand (FLT3L); thrombopoietin (TPO); and IL-3 and/or GMCSF.

A fetal stem cell-derived extracellular vesicle has immune tolerance properties. The extracellular vesicle containing a fetal stem cell-derived primal immunoglobulin contains various natural antibodies and complement proteins which can immediately respond to foreign infectious agents such as viruses, bacteria, pathogens, etc., and thus can effectively treat and prevent infectious diseases through an enhanced innate immune system. Methods are disclosed for preparing the fetal stem cell-derived extracellular vesicle.

The present invention generally relates to novel preparations of mesenchymal stromal cells (MSCs) derived from hemangioblasts, methods for obtaining such MSCs, and method sof treating a pathology using such MSCs. The methods of the present invention produce substantial numbers of MSCs having a potency-retaining youthful phenotype, which are useful in the treatment of pathologies.

In some aspects the present invention relates to engineered endothelial cells, such as E4ORF1+ ETV2+ engineered endothelial cells. In other aspects the present invention relates to methods of making such engineered endothelial cells, and methods of using such engineered endothelial cells, for example in co-culture applications.

Provided is a method of preparing a hydrogel composition including a uniform content of calcium phosphate, wherein a hydrogel composition prepared by the method has a uniform content of calcium phosphate, and thus may be used to quantify phosphates contained in the hydrogel composition. Provided is an in-vitro 3D osteoporosis model including a calcium phosphate hydrogel composition, wherein osteoblasts and osteoclasts may be three-dimensionally co-cultured inside a biogel, such that the osteoporosis model may be fabricated according to an intended use or clinical stage. Further, the model contains a calcium phosphate hydrogel with a uniform content of phosphate and thus enables quantification of calcium phosphate through measurement of phosphates, and therefore, the model may be used to screen candidate compounds for an osteoporosis drug and may effectively predict therapeutic effects of the drug on osteoporosis.

Embodiments disclosed herein concern various cells, co-cultures, methods, systems, therapies, and treatments involving in vitro and in vivo generation and use of functional mammalian thymic tissue, thymus organs, and thymic organoids. In certain embodiments, cells, tissues, and organoids disclosed herein can be used to treat a subject having a thymic condition. In other embodiments, thymic cells and organoids produced by compositions and methods disclosed herein can be used to treat various conditions, diseases, and disorders, including auto-immune disorders, transplant rejections, cancer, or aging.

The present disclosure relates to methods for expanding populations of hematopoietic stem cells (HSCs) using a genetically engineered human fetal liver niche and compositions of purified ex vivo expanded HSCs. Also provided herein are methods of using such expanded HSC cell populations for clinical applications including allogeneic hematopoietic stem cell transplantation and for drug discovery and modeling human liver development.

Compositions and methods for treating neuronal injury, such as in Parkinson's disease, comprising administration of hematopoietic stem cells and mesenchymal stromal cells to a subject are provided. Methods for producing such compositions from blood, including umbilical cord blood are also provided.