To the Editor:

A major obstacle of stem cell therapy is the risk of tumor development, a challenge addressed by Jandial and Snyder in a recent 'Bedside to Bench' article1. The writers examine our previous publication2, which describes a donor-derived brain tumor in a patient treated by experimental injection of neural stem cells; we believe their assessment underestimates the potential risks of stem cell therapy.

Jandial and Snyder question whether neural stem cells (NSCs) are at the origin of the tumor that developed1. The protocol used, similar to protocols in use at the time of treatment, is based on mitogenic growth factors and is designed to expand NSCs. Among the cultured and expanded cells given to the patient, NSCs were no doubt present, as evidenced by the documented continuous growth of the donor-derived tumors in the vicinity of the injection sites. We proved in our study by several complementary methods that the mass was composed mainly of donor-derived cells2. Even if NSCs constituted a minor fraction of the transplant, this fraction was sufficient to give rise to a tumor.

The tumor resected from our patient was diagnosed as a glioneural tumor by experienced neuropathologists. Glia and neurons, the two principal cell types comprising the central nervous system, were both represented in the tumor, and, unlike spontaneous glioneural tumors, the glial element of the subject's neoplasm was bitypic, including not only astrocytes but also ependymal cells. The cellular composition of the glioneural tumor in this case therefore strongly supports its origin from NSCs.

In agreement with our findings, Keene et al.3 recently described a donor-derived tumor, arising in a patient transplanted with intrastriatal human fetal cells, with properties similar to the one we described and to the one described by Snyder and Jandial and their colleagues in Vancouver1. The glioneural tumors from all of these patients are equivalent to the teratomas that develop from pluripotent stem cells.

Although we agree with the need for the use of very pure cell populations in future studies, improved characterization by itself will not eliminate the potential for transplanted cells to give rise to tumors.