Cumulus cell (CC) gene expression is being explored as an additional method to morphological scoring to choose the embryo with the highest chance to pregnancy. The present invention relates to a novel method of identifying biomarker genes for evaluating the competence of a mammalian oocyte in giving rise to a viable pregnancy after fertilization, based on the use of live birth and embryonic development as endpoint criteria for the oocytes to be used in an exon level analysis of potential biomarker genes. The invention further provides CC-expressed biomarker genes thus identified, as well as prognostic models based on the biomarker genes identified using the methods of the present invention.

The present invention relates generally to a three-dimensional cell and tissue culture system for the female reproductive tract. In particular provided herein the system includes individual female reproductive cultures in a dynamic microfluidic setting or integrated using a microfluidic microphysiologic system. In some embodiments, the present invention provides ex-vivo female reproductive tract integration in a three dimensional (3D) microphysiologic system.

The subject matter of the present invention is a method for differentiating epithelial stem cells, comprising culturing one or more epithelial stem cells in contact with an extracellular matrix in the presence of an expansion medium, a bovine pituitary extract, a receptor tyrosine kinase ligand, a supernatant of primary fibroblasts and optionally, a Rho kinase inhibitor.

The invention relates to placenta-derived matrix, methods of preparing, and methods of use thereof. The invention also relates to methods of culturing cells, delivering cells, promoting differentiation of stem cells or tissue-specific progenitor cells, and repairing, replacing, regenerating, filling, reducing or inhibiting scarring of defects using the same. The invention further relates to methods of coating placenta-derived matrix on a surface or injecting the placenta-derived matrix into a site of interest.

The invention relates to devices, compositions, and treatment of infertility inter alia by generating not only functional ovarian tissue but also functional oocytes from induced pluripotent stem cells. Treatments for hormone replacement are also described. In one aspect, the invention features a container including (i) a substrate; (ii) human iPSCs capable of differentiating into functional ovarian tissue; and (ii) a culture media.

The present invention relates to a composition and method for assisted reproductive technology in mammals. In particular, the present invention provides compositions and methods for in vivo maturation of an immature cumulus oocyte complex (COC), thereby enhancing the embryology outcome.

Methods for ex vivo expansion of very small embryonic like stem cells in the absence of feeder cells are provided. In some embodiments the methods include providing a plurality of VSELs; and growing the VSELs in a culture medium that includes a histone deacetylase inhibitor, luteinizing hormone, follicle-stimulating hormone, and optionally transforming growth factor beta in an amount that is sufficient to overcome quiescence of the VSELs. Also provided are feeder cell-free cell cultures, ex vivo expanded VSELs, pharmaceutical compositions that include the disclosed ex vivo expanded VSELs, methods for overcoming quiescence in VSELs, methods for re-establishing imprinting in VSELs, method for treating injuries to tissues in subjects, methods for repopulating cell types in subjects, methods for bone marrow transplantation, methods for treating radiation exposure in subjects, and methods that relate to regenerative medicine.

The present invention relates to a pharmaceutical composition comprising of preparations of human embryonic stem (hES) cells and their derivatives and methods for their transplantation into the human body, wherein transplantation results in the clinical reversal of symptoms, cure, stabilization or arrest of degeneration of a wide variety of presently incurable and terminal medical conditions, diseases and disorders. The invention further relates to novel processes of preparing novel stem cell lines which are free of animal products, feeder cells, growth factors, leukaemia inhibitory factor, supplementary mineral combinations, amino acid supplements, vitamin supplements, fibroblast growth factor, membrane associated steel factor, soluble steel factor and conditioned media. This invention further relates to the isolation, culture, maintenance, expansion, differentiation, storage, and preservation of such stem cells.

Methods of preparing ovarian tissue for primordial follicle growth are presented comprising the steps: providing an ovarian tissue sample comprising cortical tissue and stromal tissue; removing damaged tissue from the ovarian tissue sample where present; removing excess stromal tissue from the ovarian tissue sample where present; and then mechanically stretching the ovarian tissue sample along at least one dimension of the ovarian tissue sample, such that the size of the ovarian tissue sample along the at least one dimension is increased by at least 10%. Methods of growing viable oocyte in vitro, and methods of preparing individual ovarian follicles for growth are also presented.

A method of in vitro fertilization wherein the embryo is implanted into the uterus of a female patient at least two, and preferably three to twelve months after the eggs are retrieved from the patient in order to reduce the effect of autoimmune rejection of the embryo by the patient's autoimmune system and increase the probability and success of pregnancy and wherein prior to embryo implantation, the endometrium in the uterus is prepared for embryo implantation by introducing peripheral blood mononuclear cells (PBMCs) into the uterus. The procedure is combined with cryopreservation techniques to preserve the oocytes or the IVF-produced embryos of the patient.