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. ##STR00001##
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.

The present disclosure discloses a xeno-free bio-ink formulation amenable to be printed using a 3D printer. The bio-ink formulation exhibits optimum viscosity in the range of 1690-5300 cP. The present disclosure discloses a bio-printed corneal lenticule obtained from the bio-ink formulation. The bio-printed corneal lenticule as disclosed is of the optimum thickness in the range of 10-500 microns and exhibits transmittance in the range of 80-99%. The present disclosure also discloses a process for preparing the bio-ink formulation as well as for preparing the bio-printed corneal lenticule. Further, the present disclosure discloses a method of treating a corneal defect using the bio-printed corneal lenticule as an implant to treat the corneal defect. The bio-printed corneal lenticule can further be used as a model for in-vitro drug testing and diseases modelling.

Disclosed herein are methods and compositions for providing mixtures of FGF2 isoforms that are biologically active. The biological activities include, but are not limited to, stimulation of proliferation of neural precursor cells, stimulation of proliferation of endothelial cells, stimulation of development of neural precursor cells, and stimulation of development of astrocytes.

Aspects of the invention relate to a novel mesenchymal stem cell line (hb-MSC), a culture medium conditioned by the hb-MSC line, and various hb-MSC compositions. The hb-MSC compositions may include a plurality of hb-MSCs, the hb-MSC conditioned medium, or a combination thereof. The hb-MSC compositions may also include one or more of an antimicrobial agent, a film-forming agent, an appropriate carrier, as well as other additives as determined by the application. Also described are methods of use for the hb-MSC cells, the conditioned medium, and the compositions, including methods of treating or preventing bovine mastitis.

The present disclosure provides methods of producing hepatocytes from induced pluripotent stem cells. Further provided herein are methods of using the hepatocytes for the treatment of a liver disease.

Provided are new methods for generating extracellular matrix material, compositions comprising the extracellular matrix material, and methods of using the extracellular matrix.

The present disclosure discloses embodiments of a formulation for application to the cornea, the formulation comprising a hyaluronic acid, a gelatin, and exosomes. In certain variations, the exosomes may be naive mesenchymal stem cell-derived exosomes, primed mesenchymal stem cell derived-exosomes, or corneal stromal stem cell derived-exosomes. In certain variations, the primed mesenchymal stem cell-derived exosomes are exosomes derived from mesenchymal stem cells primed with a corneal stromal stem cell derived-conditioned medium.

A hanging drop device is provided in the present disclosure. The hanging drop device includes a hanging drop box and a negative pressure module. The hanging drop box includes a plate and a cover. The cover is coupled with the plate to jointly delimit a pressure chamber. The cover includes an upper surface and a bottom surface, a plurality of wells are recessed from the upper surface, and each of the wells is communicated with the pressure chamber through a hole. The negative pressure module is communicated with the pressure chamber. Each of the wells is for containing a liquid, the negative pressure module is for generating a negative pressure in the pressure chamber, so as to drive the liquid in each of the wells to pass through the hole, and the liquid forms a hanging drop hanging from the bottom surface of the cover.

The present invention relates to a method of producing cancer stem cells that comprises culturing a living cell population containing cancer cells in the presence of a gel substance to obtain a living cell population containing cancer stem cells, wherein the gel substance is a material that induces expression of osteopontin in at least a portion of cells contained in the living cell population. Moreover, the present invention relates to an agent for inducing conversion of cancer cells to cancer stem cells that comprises a gel substance that induces expression of osteopontin in at least a portion of the cells contained in a living cell population. The gel substance is a synthetic polymer gel composed of, for example, double network gel, PNaSS gel, PCDME gel, PA gel, RAMPS gel, PDMA gel or PAAc gel. The present invention provides means and a method that enable the preparation of cancer stem cells in a relatively short period of time and at a relatively low culturing cost without requiring expensive equipment.

In alternative embodiments, provided are macrocellular structures or artificially configured plurality of cells, the so-called “cardioclusters” as provided herein, comprising: a core region or cluster: comprising a plurality of first cardiac stem cells or cardiac progenitor cells; and a second region or a peripheral region positioned at least partially surrounding the outer surface of the core region or cluster, or at least partially around the core region or cluster, comprising a plurality of second cardiac stem cells; and methods for making and using them. In alternative embodiments, the second cardiac progenitor cells are cardiac progenitor cells or cardiac stem cells, mesenchymal stem cells or mesenchymal progenitor cells, or endothelial progenitor cells or endothelial stem cells.