title: Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C).
abstract: OBJECTIVE
  The aim was to evaluate cartilage regeneration in animal models involving induced knee joint damage. Through cell-mediated gene therapy methods, a cell mixture comprising a 3:1 ratio of genetically unmodified human chondrocytes and transforming growth factor beta-1 (TGF-beta1)-secreting human chondrocytes (TG-C), generated via retroviral transduction, resulted in successful cartilage proliferation in damaged regions.
  
  
  METHODS
  Non-clinical toxicology assessments for efficacy, biodistribution and local/systemic toxicity of single intra-articular administration of the cell mixture in mice, rabbits and goats was conducted.
  
  
  RESULTS
  Administration of the mixture was tolerated well in all of the species. There was evidence of cartilage proliferation in rabbits and goats. As an additional precautionary step, the efficacy of TGF-beta1 secretion in irradiated human chondrocytes was also demonstrated.
  
  
  CONCLUSIONS
  Four studies in rabbits and goats demonstrated the safety and efficacy of TG-C following direct intra-articular administration in animal models involving induced knee joint damage. Based on these pre-clinical studies authorization has been received from the USA Food and Drug Administration (FDA) to proceed with an initial phase I clinical study of TG-C for degenerative arthritis.
authors.affiliation: TissueGene Inc., Rockville, Maryland, USA.
authors.forename: Moon Jong
authors.initials: MJ
authors.lastname: Noh
authors.forename: R Ogden
authors.initials: RO
authors.lastname: Copeland
authors.forename: Youngsuk
authors.initials: Y
authors.lastname: Yi
authors.forename: Kyoung-Baek
authors.initials: KB
authors.lastname: Choi
authors.forename: Carol
authors.initials: C
authors.lastname: Meschter
authors.forename: Sally
authors.initials: S
authors.lastname: Hwang
authors.forename: Chae-Lyul
authors.initials: CL
authors.lastname: Lim
authors.forename: Vivian
authors.initials: V
authors.lastname: Yip
authors.forename: Jong-Pil
authors.initials: JP
authors.lastname: Hyun
authors.forename: Hyeon-Youl
authors.initials: HY
authors.lastname: Lee
authors.forename: Kwan Hee
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000473:pathology / Q000502:physiology; D017690:Cell Transplantation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D018014:Gene Transfer Techniques; D006041:Goats; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011817:Rabbits; D012038:Regeneration / Q000502:physiology; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1