FIG. 9.5

Where do growth factors come from?

BACKGROUND Cells can be grown outside the body in culture. However, they survive and grow well only under certain conditions. Researchers hypothesized that there are substances that are required for cells to grow in culture, but the identity and source of these substances were for a long time unknown. A key insight came from the observation that chicken cells grow much better if they are cultured in the presence of blood serum rather than blood plasma. Blood serum is the liquid component of blood that is collected after blood has been allowed to clot. Blood plasma is also the liquid component of blood, but it is collected from blood that has not clotted. American biologists Nancy Kohler and Allan Lipton were interested in identifying the source of the factor in blood serum that allows cells to survive in culture.

HYPOTHESIS Since Kohler and Lipton knew that clotting depends on the release of substances from platelets, they hypothesized that a growth-promoting factor was introduced into the blood by platelets during clotting.

EXPERIMENT 1 The investigators first confirmed earlier observations using cells that are easily grown in culture called fibroblasts, which they obtained from mice. They cultured two sets of fibroblasts in small plastic dishes. To one of the cultures they added serum; to the other culture they added plasma. Then they monitored the rate of cell division in both culture dishes over time.

RESULTS 1 They observed that the rate of cell division in the fibroblasts cultured in serum was far greater than that of the cells cultured in plasma, as expected based on earlier experiments (Fig. 9.5a).

EXPERIMENT 2 To see if the factor is released directly from platelets, they prepared a solution of proteins made from purified platelets, added these proteins to cultured fibroblasts, and measured cell growth.

RESULTS 2 They found that the solution of platelet proteins also caused the growth of fibroblasts to increase compared to the growth of fibroblasts in plasma (Fig. 9.5b).

CONCLUSION Kohler and Lipton concluded that the growth-promoting factor is a protein that is released by platelets on clot formation, and therefore normally present in serum.

FOLLOW-UP WORK Over the next few years, these and other scientists purified and characterized the growth factor we know today as platelet-derived growth factor, or PDGF.

SOURCE Kohler, N., and A. Lipton. 1974. “Platelets as a Source of Fibroblast Growth-Promoting Activity.” Experimental Cell Research 87:297–301.