be230cLecture9

Signicantly more apoptosis than control cells wt b

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Unformatted text preview: Danon Disease in Vitro Danon Pa1ent WT WT Danon UNT Starve UNT Starve LC3 ­I LC3 ­II Ac1n N Danon EB Danon iPS Cells Undergo Significantly More Apoptosis than Control Cells WT B DANON YoPro1/DAPI DANON E DCFDA/DAPI YoPro1/DAPI C WT D DCFDA/DAPI F %Apoptotic Cells * ** * ** ** ROS Levels (RFU) A ** *** *** * * ** * * * 45 Danon iPS Myocytes Have Abnormal Mitochondria 46 Danon iPS Derived Cardiomyocyte Apoptosis Improves with Treatment of Oxidative Stress 47 Fibroblast Type Clinical History Clinical Diagnosis Outcome 1 Dermal 46 yo asymptoma1c female 1st degree rela1ve of #9 n/a Pending 2 Dermal 32 yo female Normal Control  ­ ­ ­ ­ ­ ­ ­ ­ ­ 3 Dermal Cardiac 32 yo male with cardiomyopathy and skeletal muscle weakness FCM?, glycogen Storage Disease 4 Dermal 29 yo male Normal Control 5 Dermal 44 yo male with LV dysfunc1on 1st degree rela1ve of #9 FCM Medical therapy Pending 6 Dermal Cardiac 58 yo male with end stage cardiomyopathy FCM LVAD Available 7 Dermal 32 yo male with non compac1on, cardiomyopathy, SCD FCM LVNC SCD LVAD Unavailable 8 Dermal 24 yo male with lysosomal storage disease Lysosomal Storage Disease End Stage Heart Failure Unavailable 9 Dermal 14 yo male with end stage cardiomyopathy FCM LVAD OHT Available LVAD Died periopera1vely Gene1c Diagnosis Available  ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ Table 1. Descrip1on of pa1ient ­derived fibroblast cell lines. FCM=Familial Cardiomyopathy, SCD=Sudden Cardiac Death, LVAD=Lei Ventricular Assist Device, OHT=Orthotopic Heart Transplant, LVNC=Lei Ventricular Non Compac1on Using iPS Cells to Fulfill the Promise of Personalized Medicine Pluripotency-inducing factors Patient Specific Cardiomyocytes Patient Somatic cells Culture Determine If Problem of Transcription or Translation Haploinsufficiency? Dominant Negative? Enhance Gene Expression Suppress Gene Expression Using iPS Cells to Fulfill the Promise of Personalized Medicine Patient Evaluate for Phenotypic Differe...
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