This disclosure relates generally to methods for generating small hepatocyte progenitor cells (SHPCs) and hematopoietic progenitor cells (HPCs) from human embryonic stem cells, and hematopoietic progenitor cells from primary human endothelial cells and cell lines populations of small hepatocyte progenitor cells and hematopoietic progenitor cells, and uses thereof.

Long awaited is a human liver-like three-dimensional construct that makes it possible to carry out evaluation of human-specific toxicity and the like accurately and in a simple manner. The present invention provides a human liver-like three-dimensional construct comprising a heterospheroid, in which human hepatic cells and other human-derived cells which are not human hepatic cells are aggregated. This human liver-like three-dimensional construct is characterized in that the other human-derived cells are at least one selected from human hepatic stellate cells and the like, and the other human-derived cell to the human hepatic cell count ratio is at least 0.01 but less than 1.

Nucleic acid constructs and compositions that allow insertion of a FIX coding sequence into a target genomic locus such as an endogenous ALB locus and/or expression of the FIX coding sequence are provided. The nucleic acid constructs and compositions can be used in methods of introducing a F9 nucleic acid into a cell, methods of integration of a F9 nucleic acid into a target genomic locus, methods of expression of FIX in a cell, and in methods of treating hemophilia B or FIX deficiency in a subject.

Methods for derivation, culture, and maturation of small hepatic progenitor cells are described.

The present disclosure provides methods for producing bioengineered tissue along with an apparatus and other relevant compositions employed in generation thereof.

The present invention provides an endodermal cell production method that can induce differentiation of pluripotent cells into endodermal cells even when the pluripotent cells are dispersed and can achieve improved endodermal cell production efficiency. The endodermal cell production method according to the present invention is a method for producing endodermal cells by inducing differentiation of pluripotent cells into the endodermal cells, including the step of: inducing differentiation of the pluripotent cells into the endodermal cells in the presence of an endodermal cell inducing factor. In the induction step, the cell density of the pluripotent cells at the start of the induction preferably is from 0.5×10.sup.4 to 2×10.sup.4 cells/cm.sup.2.

A method for characterizing stem cell differentiation includes harvesting differentiation media supernatant containing secreted analytes from key time points during a stem cell differentiation, performing at least one of a qualitative and a quantitative analysis of the differentiation media supernatant with respect to at least one secreted analyte, and identifying trends in analyte expression based on at least one of the qualitative and quantitative analysis of the differentiation media supernatant.

Provided is a composition and an application thereof. The composition is used to prepare a medium for inducing differentiation of human pluripotent stem cells to liver precursor cells. By means of screening active components, optimizing the composition ratio and adding a GSK3-beta inhibitor, a Nodal activator, a BMP activator, a BMP inhibitor and a Hedgehog activator, human pluripotent stem cells are induced to differentiate to liver precursor cells. The process is simple and efficient, the content of positive cells is high, and the cost of cell differentiation is reduced. The invention can be used for research and application in drug development and regenerative medicinal treatment, and has broad application prospects.

A method for detoxifying a patient's blood by removing bilirubin from the patient's blood includes obtaining a batch of blood from the patient; controlling a pH of the blood so as to maintain the pH at approximately pH 7.4; controlling a temperature of the blood so as to maintain the temperature at approximately 37° C.; providing date pit-derived activated carbon; soaking the date pit-derived activated carbon within the blood for approximately 10-16 hours; and returning the detoxified blood to the patient.

In related-art methods of differentiating pluripotent stem cells into a desired cell type, there has not been established a differentiation induction method using human ES/iPS cells and being highly efficient. Many attempts have been made, including a stepwise differentiation induction method based on the control of culture conditions or the addition of, for example, various cell growth factors/differentiation factors to a culture solution, but the use of complicated culture steps is a big problem. A method of inducing differentiation into a desired cell type within a short period of time and with high efficiency by use of a pluripotent stem cell that actively undergoes cell differentiation, which is obtained by reducing an undifferentiated state of the pluripotent stem cell, has been developed, and thus the present invention has been completed.