title: Assessment of a preclinical model for studying the survival and engraftment of human stem cell derived osteogenic cell populations following orthotopic implantation.
abstract: BACKGROUND
  Preclinical studies with osteoprogenitor cells derived from human embryonic stem cells (hESC) do not lead to substantial bone regeneration in vivo. The degree of survival following implantation might play a role in their long term efficiency. We investigated the initial engraftment of hESCs-derived cells during two weeks post-implantation and compared it to such response for adult bone marrow stromal cells (hBMSC)-derived osteoprogenitor cells.
  
  
  METHODS
  hBMSC and H9-hES cells pre-treated with osteogenic factors were implanted into a calvarial defect in both adult WT and nude rats. At days 7 and 14 post-implantation, samples were analysed for persistence of implanted cells, initiation of regeneration of host bone, angiogenesis and apoptosis.
  
  
  RESULTS
  At day 7, hESC and hBMSC were detected within defects in both rat strains. By day 14 human cells were only detected in immune-deficient rats whilst still maintaining an osteoblastic phenotype and engendered a significant increase in bone formation. In WT animals, the participation of implanted cells was very limited due to their poor survival.
  
  
  CONCLUSIONS
  This study demonstrates the ability of hESC and hBMSC derived osteoprogenitor cells to survive transplantation, to engraft and to develop an osteogenic phenotype during the early stage following implantation, validating the appropriate preclinical model.
authors.affiliation: School of Science, Technology and Health, University Campus Suffolk, Waterfront Building, 19 Neptune Quay, Ipswich, UK. jordi.lopez-tremoleda@imperial.ac.uk
authors.forename: J L
authors.initials: JL
authors.lastname: Tremoleda
authors.forename: N S
authors.initials: NS
authors.lastname: Khan
authors.forename: V
authors.initials: V
authors.lastname: Mann
authors.forename: S N
authors.initials: SN
authors.lastname: Racey
authors.forename: A J
authors.initials: AJ
authors.lastname: Martin
authors.forename: A H W R
authors.initials: AH
authors.lastname: Simpson
authors.forename: B S
authors.initials: BS
authors.lastname: Noble
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*