There is disclosed a preparation of extracellular vesicles derived from human liver stem cells, preferably from a non-oval human progenitor cell line that expresses hepatic cell markers, which is capable of reducing the senescence of a population of senescent cells, as measured in a SA-β-galactosidase-based cellular senescence assay. Also disclosed are therapeutic applications of the preparation of extracellular vesicles derived from human liver stem cells according to the invention. Therapeutic applications include the reduction of cellular senescence, e.g. in an vitro or ex vivo method, as well as the therapeutic treatment of diseases and conditions known to be related to ageing and cellular senescence, such as for example atherosclerosis, diabetes mellitus type 2, asthenia, and others.

There is disclosed a preparation of extracellular vesicles derived from human liver stem cells, preferably from a non-oval human progenitor cell line that expresses hepatic cell markers, which is capable of reducing the senescence of a population of senescent cells, as measured in a SA-β-galactosidase-based cellular senescence assay. Also disclosed are therapeutic applications of the preparation of extracellular vesicles derived from human liver stem cells according to the invention. Therapeutic applications include the reduction of cellular senescence, e.g. in an vitro or ex vivo method, as well as the therapeutic treatment of diseases and conditions known to be related to ageing and cellular senescence, such as for example atherosclerosis, diabetes mellitus type 2, asthenia, and others.

A method for inducing reprogramming of a cell of a first type which is not a non-hepatocyte (non-hepatocyte cell), into a cell with functional hepatic drug metabolizing and transporting capabilities, is disclosed. The non-hepatocyte is induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte cell culture medium and hepatocyte maturation medium for a sufficient period of time to convert the non-hepatocyte cell into a cell with hepatocyte-like properties. The iHeps induced according to the methods disclosed herein are functional induced hepatocytes (iHeps) in that they express I and II drug-metabolizing enzymes and phase III drug transporters and show superior drug metabolizing activity compared to iHeps obtained by prior art methods. The iHeps thus provide a cell resource for pharmaceutical applications.

A method for inducing reprogramming of a cell of a first type which is not a non-hepatocyte (non-hepatocyte cell), into a cell with functional hepatic drug metabolizing and transporting capabilities, is disclosed. The non-hepatocyte is induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte cell culture medium and hepatocyte maturation medium for a sufficient period of time to convert the non-hepatocyte cell into a cell with hepatocyte-like properties. The iHeps induced according to the methods disclosed herein are functional induced hepatocytes (iHeps) in that they express I and II drug-metabolizing enzymes and phase III drug transporters and show superior drug metabolizing activity compared to iHeps obtained by prior art methods. The iHeps thus provide a cell resource for pharmaceutical applications.

The present application provides methods of functionalizing an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal or by culturing an organ or tissue in a bioreactor containing such nutrient. The present application also provides methods of selectively functionalizing extracellular matrix (ECM) of an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal. In some aspects, the present application provides a decellularized scaffold of a mammalian organ or tissue comprising an extracellular matrix, wherein the extracellular matrix of the decellularized scaffold is functionalized with a chemical group that is reactive in a bioorthogonal chemical reaction, such as an azide chemical group. The present application also provides biological prosthetic mesh and mammalian organs and tissues for transplantation prepared according to the methods of the application.

The present application provides methods of functionalizing an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal or by culturing an organ or tissue in a bioreactor containing such nutrient. The present application also provides methods of selectively functionalizing extracellular matrix (ECM) of an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal. In some aspects, the present application provides a decellularized scaffold of a mammalian organ or tissue comprising an extracellular matrix, wherein the extracellular matrix of the decellularized scaffold is functionalized with a chemical group that is reactive in a bioorthogonal chemical reaction, such as an azide chemical group. The present application also provides biological prosthetic mesh and mammalian organs and tissues for transplantation prepared according to the methods of the application.

The kidney regeneration accelerator that contains a component obtained by decellularizing a mammalian organ. The production method for a kidney regeneration accelerator that involves decellularizing a mammalian organ to obtain a component that includes an extracellular matrix, freeze drying and then pulverizing the component to obtain a powder, and performing a sterilization treatment on the powder. A pharmaceutical composition for use in treating kidney disease that contains a component obtained by decellularizing a mammalian organ. A treatment method for kidney disease that involves applying a pharmaceutical composition that contains a component obtained by decellularizing a mammalian organ to a site to be treated of the kidney of a human or animal kidney disease patient.

Disclosed herein are cells including pluripotent stem cells that conditionally express an immunosuppressive factor and related methods of their use and generation. In some embodiments, the cells disclosed do not express MHC I and MHC II human leukocyte antigens, and in some cases, also do not express one or more TCR complexes. In some embodiments, hypoimmunogenicity of the cells is controlled by activation of a controllable expression system upon contacting the cells with a specific factor or agent.

Disclosed herein are cells including pluripotent stem cells that conditionally express an immunosuppressive factor and related methods of their use and generation. In some embodiments, the cells disclosed do not express MHC I and MHC II human leukocyte antigens, and in some cases, also do not express one or more TCR complexes. In some embodiments, hypoimmunogenicity of the cells is controlled by activation of a controllable expression system upon contacting the cells with a specific factor or agent.

The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds within the methods of the invention. The present invention further provides cells obtainable by the methods of the invention.