Provided herein is a drug delivery device and composition, such as a particle, comprising conditioned medium. Also provided herein is a method of preparing polymeric particles for release of conditioned medium. Further, a tissue growth scaffold comprising particles for release of conditioned medium is provided.

A novel tissue usable for a kidney tissue model is provided. A method for producing a kidney-like tissue includes co-culturing a cell group containing mesenchymal stem cells, vascular endothelial cells, and clonal embryonic kidney cells.

The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or A1 and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein.

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The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula A1, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders.

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.

Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues were identified. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES.sup.+ NK cells, T-BET.sup.+ ILC1, GATA-3.sup.+ ILC2 and for IL-22.sup.+ but not for IL-17A.sup.+ ILC3. A model of tissue ILC differentiation (‘ILC-poiesis’) is proposed whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

Disclosed herein are new, useful, and non-obvious means of stimulating therapeutic angiogenesis, or conditions favorable for stimulation of therapeutic angiogenesis utilizing T regulatory cells. One disclosed method includes administering a population of T regulatory cells into an area of hypoxia to stimulate angiogenesis. T regulatory cells are generated and expanded by culture with mesenchymal stem cells, with either population or both populations together administered into the hypoxic area.

The present invention relates to a serum-free conditioned medium that solves the drawbacks mentioned in the prior art, as it does not require prior handling of the cells, and it furthermore allows starting from a large population with no additional cost. This medium favors in vitro proliferation and conservation of the pluripotency potential that allows maintaining a state that is undifferentiated with respect to the subpopulation of cancer stem cells (CSCs) and in turn does not allow survival of the differentiated cells.

The present application provides methods and processes for making and using a lyophilized mesenchymal stem cell secretome, as well as methods for treating ocular conditions and/disorders with the reconstituted lyophilized mesenchymal stem cell secretome described herein.

A method for obtaining a composition for tissue regeneration, providing M2-macrophages, co-culturing the M2-macrophages with tissue-specific cells in serum free medium; and collecting the supernatant of the co-culture. The compositions obtained by this method are suitable in medicine regenerative treatments, able to regenerate injured tissue. These products are sterile cell-free physiological aqueous solutions that show specific tissue concentration patterns to provide optimal tissue-specific regenerative effects. The compositions may be stored for long periods cryopreserved or lyophilized until its use, avoiding any subsequent blood extraction from the cell-donor, the stored growth factors and/or cytokines biologically active after long-term storage. Moreover, the compositions may be potentially applied in both autologous and allogenic treatments.

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.