OSTEOCHONDROGENIC POTENTIAL OF MARROW MESENCHYMAL PROGENITOR CELLS EXPOSED TO TGF-BETA-1 OR PDGF-BB AS ASSAYED IN-VIVO AND IN-VITRO

Mesenchymal progenitors cells can be isolated from rat bone marrow and mitotically expanded in vitro, When these cells, which we operational ly call mesenchymal stem cells (MSCs), are placed in an appropriate en vironment, they have the capacity to differentiate into bone and/or ca rtilage, This capacity is called osteochondrogenic potential, In this study, preconfluent MSCs were exposed in vitro to 5 ng/ml transforming growth factor-beta 1 (TGF-beta 1) or platelet-derived growth factor, isoform BB (PDGF-BB) for a pulse of 48 h and assayed for cell prolifer ation, alkaline phosphatase activity, and osteochondrogenic potential; untreated MSC's served as controls, In these cell culture conditions, TGF-beta 1 or PDGF-BB had similar effects on proliferation and alkali ne phosphatase activity, Both grow th factors increased cell prolifera tion and decreased alkaline phosphatase activity of MSCs. Sister cultu res of TGF-beta 1- or PDGF-BB-treated MSCs and untreated MSCs were try psinized. For each type of culture, the trypsinised MSCs were split in true parts: one part was replated in an osteogenic medium to assess i ts in vitro osteogenic potential, whereas the other part was seeded in to porous calcium phosphate ceramics and implanted subcutaneously in s yngeneic rats to assess its in vivo osteochondrogenic potential, PDGF- pretreated MSCs showed no difference in in vivo and in vitro osteochon drogenesis from that of control MSCs, while TGF-beta 1 pretreatment bl ocked the osteochondrogenic potential of MSCs when assayed in vitro fo r bone nodule formation, However, when tested in vivo, TGF-beta 1-pret reated MSCs were able to form bone and cartilage, These data show that measurements of proliferation and alkaline phosphatase activity of pr econfluent MSCs immediately after exposure to growth factor were not p redictive of their subsequent osteochondrogenic potential, Moreover, t he variation of the osteochondrogenic potential of MSCs after exposure to growth factor was further modulated by the environment in which th e MSCs were assayed.