A method for making an at least double layered cell aggregate and/or an artificial blastocyst, and/or a further-developed blastoid termed blastoid, by forming a double layered cell aggregate from at least one trophoblast cell and at least one pluripotent and/or totipotent cell, and culturing the aggregate to obtain an artificial blastocyst having a trophectoderm-like tissue that surrounds a blastocoel and an inner cell mass-like tissue. The cell aggregate can be formed from toti- or pluripotent stem cell types, or induced pluripotent stem cell types, in combination with trophoblast stem cells. Formation of a blastoid can be achieved by culturing the cell aggregate in a medium preferably comprising one or more of a Rho/ROCK inhibitor, a Wnt pathway modulator, a PKA pathway modulator, a PKC pathway modulator, a MAPK pathway modulator, a STAT pathway modulator, an Akt pathway modulator, a Tgf pathway modulator and a Hippo pathway modulator. Also, a method for growing an at least double layered cell aggregate into an artificial blastocyst, and into a further-developed blastoid, a foetus or a live animal and an in vitro cell culture comprising the mentioned compounds and/or cell aggregates.

The present invention is directed to a method of producing compositions derived from culturing cells under hypoxic conditions on a biocompatible surface in vitro. The culturing method produces both an extracellular matrix composition and a conditioned culture medium composition, which may be used separately or in combination to obtain physiologically acceptable compositions useful in a variety of medical and therapeutic applications.

The present invention relates to the generation of anterior definitive endoderm (ADE) cells from embryonic stem cells and the differentiation of such cells to, for example, pancreatic or liver cells. The invention also relates to cell lines, cell culture methods, cell markers and the like and their potential uses in a variety of applications.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

The present invention provides an artificial kidney precursor containing a non-human mammalian metanephros separated out from a living body, wherein the metanephros has been subjected to freezing and thawing treatments outside a living body, and contains mammalian mesenchymal stem cells transferred outside a living body, and a method of production thereof.

Methods and compositions for somatic cell proliferation as well as increasing viability of somatic cells are provided. The compositions include heparin binding protein isolated from a medium conditioned by growth of pluripotent stem cells, such as, human embryonic stem cells, human embryonic carcinoma cells. The methods include contacting a somatic cell with a heparin binding protein composition for a sufficient period of time to provide for enhanced proliferation and/or viability of the somatic cell as compared to the absence of the heparin binding protein composition.

Cells derived from postpartum tissue and methods for their isolation and induction to differentiate to cells of a chondrogenic or osteogenic phenotype are provided by the invention. The invention further provides cultures and compositions of the postpartum-derived cells and products related thereto. The postpartum-derived cells of the invention and products related thereto have a plethora of uses, including but not limited to research, diagnostic, and therapeutic applications, for example, in the treatment of bone and cartilage conditions.

A method for making an acellular human amnion-derived composition configured for therapeutic use is disclosed and generally includes the steps: obtaining amniotic membrane tissue; testing the amniotic membrane tissue for pathogens; washing the amniotic membrane tissue; manually removing blood-containing chorion tissue from the amniotic membrane tissue decellularizing the amniotic membrane tissue with xeno-free enzymes; collecting amniotic cells from the decellularized amniotic membrane tissue; seeding the amniotic cells for culture into xeno-free media formulated for mesenchymal stem cells; growing the amniotic cells to a specified confluency; collecting conditioned media; and freezing the collected conditioned media; wherein the method further includes irradiating the conditioned media.

Cells derived from postpartum tissue and methods for their isolation and induction to differentiate to cells of a chondrogenic or osteogenic phenotype are provided by the invention. The invention further provides cultures and compositions of the postpartum-derived cells and products such as lysates related thereto. The postpartum-derived cells of the invention and products related thereto have a plethora of uses, including but not limited to research, diagnostic, and therapeutic applications, for example, in the treatment of bone and cartilage conditions such as osteoarthritis.

Increasing therapeutic activity of fibroblasts through suppression of complement activation is disclosed. Embodiments of the disclosure teach that viability of fibroblasts in blood and/or in vivo is increased by inhibition of complement activation. In another embodiment, the blockade of complement is utilized to enhance ability of fibroblasts to suppress inflammation, stimulate generation of T regulatory cell, and inhibit pathologic T cell responses. Other enhancements of fibroblast activity disclosed as a results of complement activation include stimulation of cytokine production, release of antimicrobial and/or antiviral proteins, as well as enhancement of regenerative activities.