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SUMMARY:Could pluripotent stem cells ever be used for equine tendon regene
 ration? - Dr Debbie Guest\, Centre for Preventive Medicine\, Animal Health
  Trust\, Newmarket\, UK
DTSTART:20171011T150000Z
DTEND:20171011T160000Z
UID:TALK81011@talks.cam.ac.uk
CONTACT:Fiona Roby
DESCRIPTION:Equine pluripotent stem cells have been derived from the inner
  cell mass of blastocyst stage embryos (embryonic stem cells\, ESCs) and f
 rom the reprogramming of adult cells into a pluripotent state (induced plu
 ripotent stem cells\, iPSCs).\n\nESCs differentiate into tenocytes in vivo
  following their injection into an injured horse tendon and in vitro in re
 sponse to transforming growth factor beta 3 (TGFβ3) and/or 3D culture in 
 an anchored collagen matrix.\n\nHere we demonstrate that while equine iPSC
 s express tendon-associated genes and proteins following TGF-β3 exposure 
 in 2D culture\, they cannot remodel a 3D collagen matrix to generate “ar
 tificial tendons”. This demonstrates the utility of the 3D in vitro tend
 on assay for measuring functional tendon differentiation and the need for 
 more detailed studies to be performed to determine if epigenetic differenc
 es exist between equine iPSCs and ESCs.\n\nTo ensure the safety of pluripo
 tent stem cells in the clinic the mechanisms controlling their differentia
 tion must be understood. We have demonstrated that the transcription facto
 r scleraxis is required for tendon differentiation by equine ESCs\, as the
  overexpression of a short hairpin RNA (shRNA) to scleraxis leads to a fai
 lure to generate artificial tendons in 3D culture. Scleraxis is also requi
 red for the generation of artificial tendons by fetal tenocytes and its kn
 ockdown using shRNA results in a significant reduction in the expression o
 f COL1A1\, COMP and SOX9. These effects can subsequently be rescued throug
 h scleraxis overexpression. In contrast\, adult tenocytes expressing a shR
 NA to scleraxis demonstrated no changes in the expression levels of the ge
 nes measured and the cells continued to generate artificial tendons as nor
 mal in 3D culture. \n\nA further safety consideration is in understanding 
 the immune properties of pluripotent stem cells and their differentiated d
 erivatives. We have demonstrated that allogeneic ESCs do not produce a det
 ectable immune response following their injection into the injured tendon 
 in a small scale in vivo study. Furthermore\, undifferentiated ESCs and sp
 ontaneously differentiated ESCs do not stimulate the proliferation of co-c
 ultured allogeneic peripheral blood mononuclear cells in vitro. However\, 
 more detailed studies on the immune properties of ESC-derived tendon cells
  and the effect of an inflammatory environment are required.\n
LOCATION:Lecture Theatre 2\, Department of Veterinary Medicine
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