Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient

Abstract

BackgroundNeural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells.Methods and FindingsA boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors.ConclusionsThis is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

“…Thus, the risk of tumour initiation of transplanted cells would be increased in injured spinal cords. Actually, a positive correlation between traumatic injury and development of malignancy has recently been reported in the CNS 42 . To support this insight, RNA-seq demonstrated that NSPCs are exposed to various types of stress that could lead to DNA damage after transplantation 2 .…”

“…Recently, Amariglio et al 42 reported that transplanted NSPCs gave rise to glioneuronal neoplasms in a patient with ataxia telangiectasia. Although this report is controversial 43,44 , this highlights one of the biggest safety hurdles to overcome.…”

How stem cells speak with host immune cells in inflammatory brain diseases

“…The hypothesis of EV secretion by NPCs introduces a completely different dimension to the therapeutic applications of NPCs in regenerative medicine. By replacing transplantation of NPCs with administration of their secreted products (including EVs), many of the limitations and safety concerns associated with the transplantation of viable replicating cells, such as tumors arising from transplanted NPCs, could be mitigated (Amariglio et al, 2009). …”

Novel Treatment Strategies for Malignant Gliomas Using Neural Stem Cells

“…66 It may be prudent to have some method of eliminating the transplanted cells (or causing their terminal differentiation) after they have served their function.…”