Assessment of the malignant potential of mitogen stimulated human Schwann cells

Human Schwann cells (SCs) can be isolated and expanded with mitogens using cell culture techniques. These cells have been demonstrated to promote axon al regrowth in both the central and peripheral nervous system. Primary rat SCs can be immortalized with long-term exposure to mitogens. Transplantatio n of these cells into an autogenic host sciatic nerve results in the format ion of tumors. Human cells are, in general, relatively more resistant to ma lignant transformation, but any potential risk for inducing tumor after tra nsplantation of SCs in humans must be excluded. In this study, the malignan t potential of mitogen expanded human SCs injected into the sciatic nerve o f immunodeficient mice was investigated. Human SCs were isolated from human peripheral nerves and placed in cell culture, expanded with mitogens (here gulin and forskolin) for many passages (0-6 times), and then injected withi n the sciatic nerve of Severe Combined Immunodeficient (SCID) rat or mice. As a positive control for tumor formation in this xenograft model, human gl ioma cells were also injected. The proliferation index (PI) of the human SC s gradually decreased with each passage in cell culture. SC purity remained stable until the 6th passage, and then decreased significantly for older p assages, so that the cultures were over-grown with fibroblasts. The inciden ce for rat or human glioma cells to induce tumors was 100% and 92 %, respec tively. In contrast, there was no tumor induced by human primary or mitogen expanded SCs. Demyelination, remyelination and formation of connective she ath at the injection site were observed in some cases after injection of th e human SCs. Thus, mitogen-expanded human SCs do not produce tumors when tr ansplanted in vivo, which suggests that these cells are safe, and deserve f urther study towards their use in clinical transplantation.