Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C).
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.
Noh
Moon Jong
MJ
TissueGene Inc., Rockville, Maryland, USA.
Copeland
R Ogden
RO
Yi
Youngsuk
Y
Choi
Kyoung-Baek
KB
Meschter
Carol
C
Hwang
Sally
S
Lim
Chae-Lyul
CL
Yip
Vivian
V
Hyun
Jong-Pil
JP
Lee
Hyeon-Youl
HY
Lee
Kwan Hee
KH
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*
D053773:Transforming Growth Factor beta1