Serum activity induces Schwann cell proliferation in vitro

The present series of experiments demonstrate that a polypeptide activity present in rat serum induces a proliferative response in cultured rat Schwann cells. Schwann cells in multi-well tissue culture plates were incubated in medium containing 10% heat-inactivated fetal bovine serum and serial dilutions of normal rat serum, and control preparations were incubated in the same culture medium without rat serum. Rates of cell proliferation were assayed by measuring DNA incorporation of tritiated thymidine using liquid scintillation counting. A prominent dose-dependent proliferative response was observed among Schwann cells incubated with rat serum and rat plasma dilutions as compared to controls; this activity is abolished by heat inactivation and by proteolytic digestion, and was not affected by dialysis against a cellulose ester membrane that excludes molecules larger than 10,000 daltons. In contrast, no increase in DNA uptake of tritiated thymidine was observed when astrocyte and oligodendrocyte cultures were incubated with serial dilutions of rat serum. No proliferative effect was observed when rat Schwann cells were incubated with a dilution of standard adult bovine serum. These results suggest there is an intravascular plasma polypeptide with a molecular weight greater than 10,000 daltons that specifically stimulates Schwann cell proliferation, and it is proposed that this factor may be the mitogen responsible for the Schwann cell proliferative response known to occur after nerve injury.