Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

Genetically modified mesenchymal stem cells can be used as a medicament in the treatment of medical conditions associated with inflammation and/or an unwanted immune response in subjects without an alpha1-antitrypsin (AAT) deficiency. The stem cells include an exogenous nucleic acid, which includes (i) an Alpha-1 antitrypsin (AAT) encoding region operably linked to (ii) a promoter or promoter/enhancer combination.

Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced from pluripotent stem cells.

The present invention provides the new use of composition comprising at least one inhibitor of dipeptidyl peptidase IV (DPP-IV) for increasing migration and homing of haematopoetic progenitor cells in stem cell transplanted recipients, wherein said haematopoetic stem and/or progenitor cells had been treated in vitro with an engraftment enhancing compound, specifically with a prostacyclin analogue and a cAMP enhancer before transplantation.

The invention provides methods of preparing a sample of viable diseased cells obtained from a human subject for clinical testing, wherein the methods inhibit anoikis and/or anoikis in the cells while maintaining the physiological functions and genomic composition of the cells when they were in vivo. In the methods of the invention, primary cells are cultured in media comprising at least one anoikis inhibitor, preferably at least one inhibitor of an intrinsic anoikis pathway and at least one inhibitor of an extrinsic anoikis pathway, under anti-anoikis atmospheric conditions, such as greater than 2% and less than 20% oxygen. Method combining multiple culturing conditions, including surface attachment under conditions that inhibit anoikis, are also provided. Compositions and kits for use in the methods of the invention are also provided.

A method for preparing a stromal vascular fraction from an adipose tissue, including a step of treating an adipose tissue with an enzyme solution containing a collagenase and a neutral protease, preferably an enzyme solution free of clostripain and thermolysin, and showing not less than 1 U neutral protease activity with respect to 10,000 U collagenase activity, and recovering cells is provided by the present invention.

A method for treating a subject having a medical condition associated with inflammation and/or an unwanted immune response without an alpha1-antitrypsin (AAT) deficiency, wherein the method comprises administering genetically modified mesenchymal stem cells to the subject, wherein said genetically modified mesenchymal stem cells comprise an exogenous nucleic acid comprising (i) an Alpha-1 antitrypsin (AAT) encoding region operably linked to (ii) a promoter or promoter/enhancer combination.

Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

A method for producing a protein is provided. An objective protein is produced by culturing in a culture medium Talaromyces cellulolyticus having an objective protein-producing ability, which has been modified so that the activity of a Pep4 protein is reduced.

The present invention relates to isolated polypeptides having proteolytic activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors and host cells comprising the polynucleotides, compositions comprising the polypeptides, and methods of producing and using the polypeptides.