EFFECTS OF GROWTH-FACTORS INVIVO .1. CELL INGROWTH INTO POROUS SUBCUTANEOUS CHAMBERS

  • 1 December 1987
    • journal article
    • research article
    • Vol. 129  (3) , 601-613
Abstract
Growth factors secreted by platelets and macrophages may play roles in artherogenesis and in wound repair. The multiple biologic effects of these factors are being studied extensively in vitro, but their roles in vivo are relatively unexplored. The cellular responses to platelet-derived growth factor (PDGF), transforming growth factor beta (TGF.beta.), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) were examined in a wound chamber model in rats. Growth factors were emulsified in bovine dermal collagen suspensions, placed in 1 .times. 30-mm porous polytetrafluoroethylene tubes, inserted subcutaneously, and removed after 10 days. The presence of PDGF (400 ng), TGF.beta. (200 ng), or bFGF (100 ng) increased the DNA content of the chambers two- to sixfold, compared with controls. Regardless of dose, EGF (100-800 ng) did not affect the DNA content. The increases in DNA observed for PDGF, TGF.beta., or bFGF resulted from accumulations of varying numbers of fibroblasts, capillaries, macrophages, and leukocytes in 10-day chambers. The addition of 250 .mu.g/ml heparin to the collagen suspension potentiated the response to PDGF and by bFGF, but not to TGF.beta. or EGF. The clearance of 125I-labeled growth factors from the chambers was biphasic. After an initial rapid phase, the remaining growth factor was slowly cleared. The half-life of the initial phase was rapid for PDGF (12 hours) and bFGF (9 hours) and somewhat slower for TGF.beta. (22 hours). There was no difference in the rate of clearance between collagen and collagen/heparin matrices for any of the growth factors examined. These studies demonstrate that PDGF, bFGF, and TGF.beta. can induce granulation tissue development in normal animals. The similarity in cellular responses to three peptides with differing in vitro actions suggests that the responses observed at 10 days reflect a secondary process, possibly mediated by effector cells such as macrophages, lymphocytes, or granulocytes that are attracted into the chamber by each growth factor, rather than a direct effect of the factors themselves.