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UCONN - PNB 3260 - Class Notes - Week 4

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UCONN - PNB 3260 - Class Notes - Week 4

School: University of Connecticut
Department: Physiology
Course: Stem Cell Biology
Professor: Conover
Term: Spring 2016
Tags: PNB 3260
Name: PNB 3260 Week 4 notes
Description: Lecture 7 and 8
Uploaded: 02/10/2016
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background image Week 4 PNB 3260 Lecture Notes   Lecture 7 - Student talks on papers   
Therapeutic Translation of iPSCs for treating neurological disease 
History    neurogenetic disorders modeled first then sporadic disease  Patterns in specific diseases    important for modeling    synaptic defects are different in vivo    Bench and Bedside = working with clinicians  Targeted Genome Modification    goal: find similarities between disease phenotype in the lab (dish) and in vivo    Challenge to goal - lower variability    worst to best    ZFNs (zinc-finger nucleases)  TALENs (transcription activator-like effector nucleases)  CRISPR/Cas system - clustered regularly interspaced palindromic repeats    can use more than one mutation  if diseases aren't genetic (they are sporadic) harder to model because it's complex 
lineage specific cells can be used for sporadic cases 
Neighboring cells 
  important to consider role of neighboring cells    use other fields to learn about entire environment of the cells  Microfluidics    3D growth    allows multiple lines to be grown at once    were able to differentiate half and leave half undifferentiated - ability to choose    helps look at bigger picture: structure and function rather than single cell basis  Microelectrode Array     record activity between dif populations of neurons    can be combined with microfluidics    useful for long-term culturing    limitation: accessibility- can't record intracellular potentials  iPSC applications    ultimate goal: total regeneration of disease tissue    other goals:   drug development    only 10% make it past safety concerns to be tested    benefits of iPSCs in drug specificity     disease specificity    human specificity     high-throughput screening (HTS) - conduct multiple tests at 
once 
Transplantation therapies    human fetal neural stem cells (fNSCs)    may not work as well as iPSCs    Retinal degeneration    differentiated ESC and iPSC to functional rod photoreceptors    no tumorgenesis in this study    no immunorejection  Bench to Bedside    Perfecting cell line's safety and efficacy   In Vivo reprogramming in humans    transdifferentiation of cells 
background image   fibroblasts and astrocytes from humans  put in 3 growth factors: Ascl!!, Brn2a, Myt1l  became neuronal cells  ipscs in clinical and commercial area    commercial  mostly based of unsubstantiated data   
Stem Cell Reports - PAPER #2 
iPSCs to treat ALS in mice 
  degeneration of upper and lower motor neurons    mostly contralateral but also ipsilateral corticospinal tract  mSOD1 mutation    associated with familial     associated with ~20% sporadic cases  2 main hypotheses 
1) Glia play a significant enough role in the ALS phenotype that manipulating these cell types will 
have an observable effect;  
2) hiPSCs can be used to generate glial cells that will effectively replace those damaged in ALS, and 
restore normal glial functionality. 
 
hiPSC-GRNPs 
  glial rich neural progenitors  Some mice got hiPSC-GRNPs then littermates got PBS control  Male mice had better improvements but died earlier than female mice 
introduction into in vivo increased amount of neurotrophic factors present 
mSOD1 induces oxidative stress 
  males may be more vulnerable to this stress  VEGF caused enhanced blood vessel production?    VEGF may be reason for increased life span  Study would have had to continue longer to prove it doesn't result in tumorgenicity     

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School: University of Connecticut
Department: Physiology
Course: Stem Cell Biology
Professor: Conover
Term: Spring 2016
Tags: PNB 3260
Name: PNB 3260 Week 4 notes
Description: Lecture 7 and 8
Uploaded: 02/10/2016
4 Pages 28 Views 22 Unlocks
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  • 24/7 Homework help
  • Notes, Study Guides, Flashcards + More!
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