Induced extended pluripotent stem cells, method of making and using

A cell culture media composition for extending cell potency of isolated pluripotent cells, the composition comprising chemical extenders of pluripotency (CEP) from each of the following groups

• (1) a cytokine,
• (2) a glycogen synthase kinase (GSK) inhibitor,
• (3) a G protein coupled receptor (GPCR) inhibitor
• (4) a Poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, and
• (5) optionally, Rho-associated, coiled-coil containing protein kinase (ROCK) inhibitor,
• in amounts effective to induce reprogramming of an untreated cell, into an extended pluripotent cell,
• and optionally wherein
• (a) the cytokine is selected from the group consisting of human inhibitory fact (LIF, “L”), interleukin (IL)-6, IL-11, IL-27, IL-31, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, neuropoietin and cardiotrophin-like cytokine factor 1;
• (b) the GSK inhibitor is a GSK3 inhibitor, and more preferably the GSK inhibitor is selected from the group consisting of CHIR99021 (“C”) [6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino]-3-pyridinecarbonitrile];
• BIO-acetoxime;
• GSK 3I inhibitor XV;
• SB-216763;
• CHIR 99021 trihydrochloride;
• GSK-3 Inhibitor IX [((2Z, 3E)-6′-bromo-3-(hydroxyimino)-[2,3′-biindolinylidene]-2′-one];
• GSK 3 IX [6-Bromoindirubin-3′-oxime];
• GSK-3β Inhibitor XII [3-[[6-(3-Aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenol];
• GSK-3 Inhibitor XVI [6-(2-(4-(2,4-dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)-pyrimidin-2-ylamino)ethyl-amino)-nicotinonitrile];
• SB-415286 [3-[(3-chloro-4-hydroxyphenyl)amino]-4-(2-nitrophenyl)-1H-pyrrole-2,5-dione];
• and Bio [(2′Z,3′E)-6-bromoindirubin-3′-oxime];
• (c) the GPCR inhibitor is an acetylcholine receptor antagonist, and more preferably the GPCR inhibitor is DiM ((S)-(+)-Dimethindene maleate) (“D”);
• and/or
• (d) the PARP1 inhibitor is selected from the group consisting of MiH (Minocycline hydrochloride) (“M), BSI-201 (4-iodo-3-nitrobenzamide), NAM (Nicotinamide), PJ34 (N-(6-Oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide;
• PARP Inhibitor XIV;
• 4-[(1-Methyl-1H-pyrrol-2-yl)methylene]-1,3(2H,4H)-isoquinolinedione;
• Veliparib;
• 2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide dihydrochloride;
• Olaparidb (1-(Cyclopropylcarbonyl)-4-[5-[(3,4-dihydro-4-oxo-1-phthalazinyl)methyl]-2-fluorobenzoyl]piperazine);
• 6-amino-1H-benz[de]isoquinoline-1;
• and INH2BP (5-Iodo-6-amino-1,2-benzopyrone).