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The Two Tort Dit U Nani Minuta Omulutni THETWO TORT DIT USU 20180273906A1NANI MINUTA OMULUTNI ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2018/ 0273906 A1 Ashraf (43 ) Pub . Date : Sep . 27 , 2018 ( 54 ) MICROVESICLE AND STEM CELL Publication Classification COMPOSITIONS FOR THERAPEUTIC (51 ) Int. Cl. (54 ) COMPOSATIONSAPPLICATIONS C12N 57074 (2006 .01 ) C12N 5 / 077 ( 2006 . 01) (71 ) Applicant: Muhammad Ashraf, Cincinnati , OH C12N 5 /071 (2006 . 01 ) (US ) A61K 35 / 12 ( 2006 .01 ) ( 72 ) Inventor: Muhammad Ashraf , Cincinnati, OH (52 ) U . S . CI. CPC . .. C12N 5 / 0696 ( 2013 .01 ) ; C12N 5 /0657 (US ) (2013 .01 ) ; C12N 2506 / 45 ( 2013 .01 ) ; C12N (21 ) Appl. No .: 15 / 881, 693 570661 ( 2013 .01 ) ; A61K 35 / 12 ( 2013. 01 ) ; C12N 5 / 069 ( 2013 . 01 ) ( 22 ) Filed : Jan . 26 , 2018 Related U . S . Application Data (57 ) ABSTRACT (63 ) Continuation - in -part of application No . 14 / 255, 789, Provided herein are stem cell and exosome compositions filed on Apr. 17 , 2014 , Continuation - in - part of appli having therapeutic utility to treat a variety of diseases and (63 ) Condcation on No Apr . .14 17 / 951, 20152 , 354 , filed onon Nov;. 5201 24 , 2015, 292 , Con file disorders , e . g . , cardiovascular disease , Duchenne muscular tinuation - in -part of application No . 15 / 201, 292 , filed dystrophy , and fibrotic disease . on Jul. 1 , 2016 . Specification includes a Sequence Listing . Patent Application Publication Sep . 27 , 2018 Sheet 1 of 56 US 2018 /0273906 A1 Mergest BAX : 2:5 . * 7:22 . .2 .: . W . Nanog FIG . 1 111111111111111111111111111111111111111111111111VVVVVVVVVVVVVVVV Patent Application Publication Sep . 27 , 2018 Sheet 2 of 56 US 2018 /0273906 A1 : : : ????????????????????? 8 8 DNMTinhibition% 8 . 8 8 o wwwwwwwwwwwwwwwwwwwwwwwwwww wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww Non treated IPS Small molecule - IPS FIG . 2 Patent Application Publication Sep . 27 , 2018 Sheet 3 of 56 US 2018 /0273906 A1 DAP JUNOY Merced . * . ? ?????? , .. .. ::: .. * . .. **** - :. : . :. :. :. .: : . + .. SEON .. .:1 +1 + : 1 . ::111 **: :1, 1 .1. 1+ .. : an ri * 7 . Vm . * XV. i . i ..: : . : . :: SasaWIS . FIG . 3A Absorbance490nm 1.11 :# + + + + IiIi - + + + . II. 1 +!1 ! !! + + ++ + 11! ? ! ? + ++ + - + .- ! * + + - IIIY ++ - -II. + + * !! 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SE * < 0 . 05 en os CardiacFunction(%) mahamannannnnnnnnnnnnnnnn mwanaume wallet EF (1 % ) FS ( % ) FIG . 8F Heterogeneous BMSCs SJSCS 10 um FIG . 9A Patent Application Publication Sep . 27, 2018 Sheet 10 of 56 US 2018 /0273906 A1 . ' . ' . ' . ' . ' . ' . ' . ' . ' . ' . 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Nkx2.5 Meta Gapdh * Mef2cNkx26 w * Aged * FIG.SE * Gatau (uodes o pozjeudou ) vosso do angeon * * * * * * * * * * * * ws W Rex- Gapoh Oct Nanog KIEM wwwww Oc14NanogSox2K:14Rex1 . ** * ** * * * ** * ** * * ** * * * * * * «* Aged W SJSCBMSC s wiwiwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww FIG.9D S (updeg oj pozjewou ) expression Relative Patent Application Publication Sep . 27, 2018 Sheet 13 of 56 US 2018 /0273906 A1 Agent SUSOSBMSCSSJSCS w FIG.91 wwwwwwwww firmox . ) 60( vai BMSCS 000 Wow Aged FIG.9G 0000000000000 SJSCS Aged NYUV wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww Bugal wwwwwwwwwwwwwwwwwwwwwwwwwwwwwww FIG.9H VOM ?????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????voj gubew Patent Application Publication Sep . 27, 2018 Sheet 14 of 56 US 2018 /0273906 A1 * * * .. 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NO. * . * . * . * . * . * . * . * . * . * . * . * . * . * www * * * * * * * * * * * . w wwwwwwwwwwwwwwwwwwwww4444444444444 Posteriou Otak* * * * * * * * * * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * * * * * * * * * * ** * * Vias ** * ** * * ** * * * * ** * ** * ** * * * * * * * * FIG . 11A Eles Eles . CTGF Actin N 0037 M Caca) * 003Boeta poyo MIOVE90( www. ( www Eles de la 03 FIG . 11B FIG . 11C Nom eles bles ?? ? ?? ? ? ? ? ? ? ?? ? ? ? ?? ? ?? ? ? ? ? ? ?? ? ? ? ?? ?? ?? ? ?? ?? ?? ? Merged with DANI CIGA Merced with DARI FIG . 110 Patent Application Publication Sep . 27 , 2018 Sheet 17 of 56 US 2018 /0273906 A1 transton region 3 UIR ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? ???? 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Luciferaseactivity(14) xemtie MR 19% Peluamimi VIR FIG . 12D - Cumhem m hentiLenti -miR - -195 195 inhibitorinhibito Lenti scramble FIG . 13A Patent Application Publication Sep . 27 , 2018 Sheet 19 of 56 US 2018 /0273906 A1 * OMSCs * ** MOMSCs Adevou 9- wwwww * OMSCS WOMSCX FIG . 13B XOMSCS * * * ** SOMSCS * * * .:. wwwwwww Sows Wwwwwwwwwwwwwwwww . wwwmmmmmmmmmmm MOUSE MOUSC FIG . 13C Patent Application Publication Sep . 27, 2018 Sheet 20 of 56 US 2018 /0273906 A1 SCIOMSCS anu -195OMSCS YYYYYYYYYYYYYY WWWWWWWWWWWWwwwhere the two other two wwwwwwwwwwwwwwwwwwwwwwww :LE 00000000000000000 * TUNELcells stagjezov .. .. .. .. .. .. scramble anti-miR - 195 FIG . 13D Patent Application Publication Sep . 27, 2018 Sheet 21 of 56 US 2018 /0273906 A1 SIOMSC $ 19OMSC : TERE SIRI FOXO1 FOXO1 AKT 8023 Cleavad Caspase 3 40B FIG . 13E * * * * * * * * * * * * * * * * * * * * * * * * iren SOMSCS COLX)Bello * * * -19SONSCS Culonyformation(9 * **** standartinis in.. ???? ?? ???? ???? days SOOMSC - CONSC FIG
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