Abstract: Provided is a method of in vitro generating functional hPSC-islets, comprising a step of generating pancreatic endocrine progenitors from pancreatic progenitors by using a medium supplemented with ISX9 or a combination of ISX9 and Wnt-C59. Also provided are media used in the method, a population of cells including functional hPSC-islets generated by the method and uses thereof.

Abstract: Provided are chemical inducers of pluripotency (CIP) which include glycogen synthase kinase inhibitors, TGF? receptor inhibitors, cyclic AMP agonists and S-adenosylhomocysteine hydrolase (SAH) inhibitors or histone acetylators. A method of inducing pluripotency in a partially or completely differentiated cell by using such chemical inducers of pluripotency is also provided. The method includes: (i) contacting a cell with the CIPs for a sufficient period of time to result in reprograming the cell into a pluripotent stem cell having ESC-like characteristics (CiPSC). Isolated chemically induced pluripotent stem cells (CiPSCs) and their progeny, produced by inducing differentiation of the CiPSCs, can be used in a number of applications, including but not limited to cell therapy and tissue engineering.

Abstract: Provided are chemical inducers of lineage reprogramming (CiLR) which include glycogen synthase kinase inhibitors, TGF? receptor inhibitors, cyclic AMP agonists or histone acetylators. Also provided is a method of inducing lineage reprograming in a partially or completely differentiated cell of a first type into a cell with characteristics of a second and different lineage. The method includes: contacting a cell with the CiLR for a sufficient period of time to result in reprograming the cell into a modified XEN-like cell which is subsequently programmed into a cell with characteristics of a second and different lineage.

Abstract: Compositions of culture conditions and the stepwise method for improving reprograming of human somatic cells into human chemically induced pluripotent cells are disclosed. The first stage, which uses a combination of small molecules with necessary biological activities, is aimed at downregulating the somatic gene program. The second stage uses a selection of small molecules with select biological activities to upregulate one or more pluripotency-related transcriptional factors. The third stage uses a selection of small molecule factors with select biological activities to establish an initial pluripotency network, measured by the expression of OCT4. The fourth and final stage uses a selection of small molecules with select biological activities to fully establish a pluripotent network, measured by co-expression factors such as OCT4, SOX2, and NANOG in the reprogrammed cells. The resultant reprogrammed cells are termed human chemically induced pluripotent stem cells, hCiPSCs.

Abstract: 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.

Abstract: Senolytic and anti-inflammatory prodrugs are provided, which are designed from a cytotoxic agent, by chemically modifying the cytotoxic agent to incorporate a site cleavable by SA-?-gal following delivery of the prodrug in vivo, to release the active parent drug. The prodrug includes a galactose-based moiety, which is preferably acetylated, and benzyl oxy carboxy group and a cytotoxic agent moiety. The selenolytic prodrug is used to selectively kill one or more senescent cells and/or reduce an acute or chronic inflammatory response in a subject in need thereof, by administering to the subject therapeutically effective amount of the senolytic prodrugs. The disclosed compositions can be used to reduce one or more symptoms associated with a Senescence-associated disease or disorder or an inflammatory disorder, for example, a virus-mediated inflammation, in a subject.

Abstract: Provided are compositions for long-term maintenance of functional hepatocytes in culture, a method for improved maintenance of functional hepatocytes in vitro, and functional hepatocytes cultures according to the methods. The culture compositions include at least: one activator of adenylate cyclase, one TGF? inhibitor, one Notch inhibitor, one Wnt inhibitor, and/or one BMP inhibitor. The combinations of compounds are added to any hepatocyte cell culture medium in an effective amount to maintain functional hepatocyte function in vitro, long term. The hepatocytes can be used for in vitro drug research and to model liver disease.

Abstract: A method for inducing non-hepatocytes into hepatocyte-like cells, wherein the non-hepatocytes are induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte expansion culture medium and 2C medium for a sufficient period of time to convert the non-hepatocyte cell into cells with hepatocyte-like properties, are provided. The iHeps induced according to the methods are also provided.

Abstract: Provided are chemical inducers of pluripotency (CIP) which include glycogen synthase kinase inhibitors, TGF? receptor inhibitors, cyclic AMP agonists and S-adenosylhomocysteine hydrolase (SAH) inhibitors or histone acetylators. A method of inducing pluripotency in a partially or completely differentiated cell by using such chemical inducers of pluripotency is also provided. The method includes: (i) contacting a cell with the CIPs for a sufficient period of time to result in reprograming the cell into a pluripotent stem cell having ESC-like characteristics (CiPSC). Isolated chemically induced pluripotent stem cells (CiPSCs) and their progeny, produced by inducing differentiation of the CiPSCs, can be used in a number of applications, including but not limited to cell therapy and tissue engineering.

Abstract: Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.

Abstract: SUSD2 protein is used as a marker in identification, selection or separation of pancreatic internal secretion precursor cells and/or newborn pancreatic internal secretion cells; and a use of an mRNA, for encoding the SUSD2 protein, of a precursor protein as the marker in identification of the pancreatic internal secretion precursor cells and/or the newborn pancreatic internal secretion cells. Analysis of gene expression of pancreatic endoderm cells sourced by induced directional differentiation of human pluripotent stem cells finds the enrichment expression of a SUSD2 gene in the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells. A protein encoded by the SUSD2 gene is a receptor protein on cell membranes. Using the protein as the marker, the identification, the selection or the separation of the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells can be conducted.

Abstract: Cocktails of chemical inducers of neuron-like properties (CINP) is provided, which includes cAMP agonists, neurogenic small molecules, glycogen synthase kinase inhibitors, TGF? receptor inhibitors, and BET family bromodomain inhibitors and optionally, a selective inhibitor of ROCK or p38 MAPK. These cocktails are used in a method of inducing neuron-like properties in partially or completely differentiated non-neuronal cells. The method includes contacting cells of a first type (non-neuronal) with the CINPs for a sufficient period of time to result in reprogramming the cell into cells of a second type having neuron-like characteristics (CiNs). Isolated chemically induced neurons (CiNs) can be used in a number of applications, including but not limited to cell therapy.

Abstract: Provided are chemical inducers of lineage reprogramming (CiLR) which include glycogen synthase kinase inhibitors, TGF? receptor inhibitors, cyclic AMP agonists or histone acetylators. Also provided is a method of inducing lineage reprograming in a partially or completely differentiated cell of a first type into a cell with characteristics of a second and different lineage. The method includes: contacting a cell with the CiLR for a sufficient period of time to result in reprograming the cell into a modified XEN-like cell which is subsequently programmed into a cell with characteristics of a second and different lineage.

Abstract: Provided are chemical inducers of pluripotency (CIP) which include glycogen synthase kinase inhibitors, TGF? receptor inhibitors, cyclic AMP agonists and S-adenosylhomocysteine hydrolase (SAH) inhibitors or histone acetylators. A method of inducing pluripotency in a partially or completely differentiated cell by using such chemical inducers of pluripotency is also provided. The method includes: (i) contacting a cell with the CIPs for a sufficient period of time to result in reprogramming the cell into a pluripotent stem cell having ESC-like characteristics (CiPSC). Isolated chemically induced pluripotent stem cells (CiPSCs) and their progeny, produced by inducing differentiation of the CiPSCs, can be used in a number of applications, including but not limited to cell therapy and tissue engineering.

Abstract: Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.

Abstract: Cocktails of chemical inducers of neuron-like properties (CINP) is provided, which includes cAMP agonists, neurogenic small molecules, glycogen synthase kinase inhibitors, TGF? receptor inhibitors, and BET family bromodomain inhibitors and optionally, a selective inhibitor of ROCK or p38 MAPK. These cocktails are used in a method of inducing neuron-like properties in partially or completely differentiated non-neuronal cells. The method includes contacting cells of a first type (non-neuronal) with the CINPs for a sufficient period of time to result in reprogramming the cell into cells of a second type having neuron-like characteristics (CiNs). Isolated chemically induced neurons (CiNs) can be used in a number of applications, including but not limited to cell therapy.

Abstract: The invention provides a composition and a method for inducing pluripotency in non-pluripotent eukaryotic cells. The composition comprises chemical inducers of pluripotency (CIPs) including glycogen synthase kinase (GSK) inhibitors, TGFp receptor inhibitors, cyclic AMP agonists, S-adenosylhomocysteine hydrolase (SAH) inhibitors, and optionally an agent that promotes histone acetylation. The method comprises contacting a cell with the CIPs for a sufficient period of time to reprogram the cell into a pluripotent stem cell.

Abstract: SUSD2 protein is used as a marker in identification, selection or separation of pancreatic internal secretion precursor cells and/or newborn pancreatic internal secretion cells; and a use of an mRNA, for encoding the SUSD2 protein, of a precursor protein as the marker in identification of the pancreatic internal secretion precursor cells and/or the newborn pancreatic internal secretion cells. Analysis of gene expression of pancreatic endoderm cells sourced by induced directional differentiation of human pluripotent stem cells finds the enrichment expression of a SUSD2 gene in the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells. A protein encoded by the SUSD2 gene is a receptor protein on cell membranes. Using the protein as the marker, the identification, the selection or the separation of the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells can be conducted.

Abstract: 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.

Abstract: Provided is a cocktail of factors for converting/reprogramming non-naïve pluripotent stem cells into TGF? signaling-independent (TSI) naïve induced pluripotent stem cells (iPSCs). Also provided are methods for reprograming a non-naïve PSC into a TSI naïve iPSC by contacting the cell to be reprogrammed with effective amounts of compounds for a sufficient period of time to reprogram the cell into a TSI naïve iPSC.