The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

An exemplary method can be provided for producing ureteric bud cells from pluripotent stem cells, in vitro. Further, an exemplary method can be provided for producing ureteric bud cells and Wolffian duct (WD) progenitor-like cells that are a progenitor of the ureteric bud cells. Another exemplary method can be provided for producing Wolffian duct (WD) progenitor-like cells that can comprise obtaining C-X-C chemokine receptor 4 (CXCR4) positive and KIT proto-oncogene receptor tyrosine kinase (KIT) positive cells. In addition, an exemplary method can be provided for producing ureteric-bud-like cells using WD progenitors that are CXCR4+ and KIT+, and another exemplary method can be provided for producing kidney organoids in which the ureteric-bud-like cells can be used.

Provided is a method for culturing immature oocytes. The method can promote in vitro maturation of the immature oocytes, and specifically comprises using follicular cells and a culture medium for culturing same. The culture medium for culturing the follicular cells contains CNP or variants thereof or analogues thereof and an HDAC (histone deacetylase) inhibitor. Also provided are the in vitro maturation culture medium containing CNP or variants thereof or analogues thereof and the HDAC inhibitor, and related compositions thereof, and the use of the above medium, culture medium and compositions in the promotion of in vitro maturation of the immature oocytes.

Provided is a method for inducing differentiation of neural crest cells into neurons of the autonomic nervous system, the method including the step of culturing neural crest cells in the presence of at least one of a BMP signaling pathway activator, an SHH signaling pathway inhibitor, and a Wnt signaling pathway inhibitor.

Methods and systems for enhancing cell populations such as chondrocytes for tissue engineering applications, e.g., for production of neocartilage. The methods and systems of the present invention feature the introduction of a hypotonic buffer to the cells during the cell isolation process, which results in neotissue (e.g., neocartilage) constructs that are significantly more mechanically robust as compared to those not treated with hypotonic buffer. The methods and systems may further comprise introducing cytochalasin D to cells purified with a hypotonic buffer, which can further bolster the mechanical properties and matrix deposition of the cells. The methods and systems result in neocartilage engineered from chondrocytes, for example, from fetal aged tissue, having compressive properties on par with native adult articular cartilage.

A new use of exosomes extracted from mesenchymal stem cells derived from a healthy individual co-cultured with melatonin or a culture solution thereof, for the treatment of chronic kidney disease is disclosed. A pharmaceutical composition containing the exosomes extracted from mesenchymal stem cells derived from a healthy individual co-cultured with melatonin or a culture solution thereof as an active ingredient and a method for preparing the pharmaceutical composition are disclosed. The exosomes promote the proliferation of mesenchymal stem cells derived from a chronic kidney disease patient or increase the survival rate of the patient.

A problem of this invention it to provide a method for differentiate a primordial germ cell into a functional GV stage oocyte by in vitro culture. This invention relates to a method for differentiating a primordial germ cell into a functional GV stage oocyte by in vitro culture, comprising: (a) a step of producing a secondary follicle by culturing the primordial germ cell and supporting cells adjacent to the primordial germ cells under conditions that eliminate the effects of estrogen or a factor having a similar function to estrogen; (b) a step of partially dissociating cells between a granulosa cell layer and a thecal cell layer, wherein an oocyte, the granulosa cell layer, and the thecal cell layer constitute the produced secondary follicle; and (c) a step of differentiating the oocyte into a functional GV stage oocyte by culturing the oocyte, the granulosa cell layer, and the thecal cell layer that constitute the secondary follicle in a medium containing a high-molecular-weight compound.

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 disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.