The invention relates to cell-free compositions obtained by culturing adult-derived human liver stem/progenitor cells (ADHLSC) in cell culture medium and isolating the resulting conditioned medium (ADHLSC-CM) that has advantageous properties, such as anti-fibrotic effects. ADHLSC-CM, compositions based on ADHLSC-CM, and other related and derived products, can be used in cell culture processes or as a medicament, more particularly for the treatment of diseases involving organ injury, organ failure, in organ or cell transplantation or the pathological disruption, inflammation, degeneration, and/or proliferation of cells within a tissue or an organ, in particular within liver.

This application describes liver stem cells (LSC), and differentiated hepatocytes, cholangiocytes, and 3D cellular structures derived therefrom. Methods for producing LSC and mature, differentiated hepatocytes and cholangiocytes in culture are provided. Also provided are cell culture systems and cell culture media for producing a homogenous population of liver stem cells that remain in an undifferentiated state over multiple passages in culture. The LSC and methods are useful for producing homogenous populations of hepatocytes and cholangiocytes for downstream applications. The LSC can be transplanted into subjects to treat liver diseases.

A method of constructing a hepatic precursor-like cell line is provided. The deposited number of the hepatic precursor-like cell line is CCTCC NO: C2019120. The construction method includes using primary hepatocytes as seed cells to establish the hepatic precursor-like cell line, which combines with controlling the conditions of passage culture, subculture, virus infection, proliferation culture and confluence culture. Moreover, a hepatocyte-specific transcription factor, FOXA3, is expressed in the immortalized cell line to make the hepatic precursor-like cell line differentiate easily. An application of the hepatic precursor-like cell line in the field of the bioartificial liver is also provided.

A production method for a proliferative liver organoid includes culturing liver stem cells or a tissue fragment including liver stem cells in a growth medium to obtain a proliferative liver organoid, in which the growth medium contains an interleukin-6 family cytokine. A production method for a metabolically activated liver organoid includes culturing the proliferative liver organoid produced by the production method for a proliferative liver organoid in a differentiation medium to obtain a metabolically activated liver organoid, in which the differentiation medium does not substantially contain an interleukin-6 family cytokine.

The invention relates to a process for the manufacture of a population of human allogeneic liver-derived progenitor cells (HALPC), comprising the use of microcarriers and a bioreactor.

The invention relates to a process for the manufacture of a population of human allogeneic liver-derived progenitor cells (HALPC). The process comprises the use of a xeno- and serum-free culture medium comprising purified native or recombinant human serum albumin.

The invention relates to a method for inducing human cholangiocyte differentiation of progenitor cells called hepatoblasts. More specifically, the invention relates to a method for differentiating hepatoblasts to cholangiocytes by culturing said hepatoblasts with a particular medium having interleukin-6 (IL-6) activity. The differentiation method can specifically induce cholangiocyte dilferentiation from hepatoblasts, and the human cholangiocytes differentiated according to the invention may be useful for drug discovery for treatment of cholangiopathies and bioengineered livers.

The invention relates to a liver organoid, uses thereof and method for obtaining them.

The invention relates to a method for inducing human cholangiocyte differentiation of progenitor cells called hepatoblasts. More specifically, the invention relates to a method for differentiating hepatoblasts to cholangiocytes by culturing said hepatoblasts with a particular medium having interleukin-6 (IL-6) activity. The differentiation method can specifically induce cholangiocyte differentiation from hepatoblasts, and the human cholangiocytes differentiated according to the invention may be useful for drug discovery for treatment of cholangiopathies and bioengineered livers.

Active loading of extracellular vesicles (EVs) with an exogenous molecule without damaging the extracellular vesicles is provided. A composition comprising a population of extracellular vesicles loaded with an exogenous molecule, which have maintained their integrity, original endogenous cargo and functionality, compared to unloaded controls is also provided. Extracellular vesicles are derived from a stem cell, preferably an adult stem cell, or from a biological fluid, a conditioned cell medium or a tissue culture medium.