Tumor Formation Following Murine Neural Precursor Cell Transplantation in a Rat Peripheral Nerve Injury Model

Abstract

Neural stem cells show a remarkable aptitude for integration and appropriate differentiation at sites of cellular injury in central nervous system (CNS) disease models. In contrast, reports of neural stem cell applications in peripheral nerve injury models are sparse. In this study we sought to determine if the C17.2 cell line would respond to cues in the microenvironment of the injured peripheral nerve and enhance neuronal regeneration in rodent sciatic nerve injury models. We transplanted C17.2 into several sciatic nerve injury models in 45 nude rats, including nerve transection, nerve crush, and nerve gap models. Twelve of the animals in this study developed large tumors at the site of neural stem cell transplants. Histologically, the tumors resembled neuroblastomas. The tumors were confirmed to be of transplanted cell origin by positive beta-galactosidase staining. Tumors occurred only in models where the nerve remained intact or where continuity of the nerve was restored. We concluded that C17.2 transplantation into peripheral nerve injury models resulted in a high rate of tumor formation. This study demonstrates that the success of neural precursor transplants in the CNS cannot necessarily be extrapolated to the peripheral nervous system.

The Delayed Repair of Sciatic Nerve Defects with Tissue-engineered Nerve Grafts in Rats

“…However, the number of transplanted NSCs was very low, for example, about 0.5-1% NSCs after 4 months for transplantation; furthermore, most of the surviving NSCs remain undifferentiated, and all express nestin, a stem cell marker [27]. Even more, a recent study [32] revealed that grafting of NSCs into injured peripheral nerve stimulated tumor formation, despite no identical observation in our study. In our experiment, chitosan/PGA conduits are likely suitable for delayed repair of peripheral nerve defects, and additional enhancement by introduction of NSCs must be dependent on many complex conditions, including the cell density of added NSCs, the way of introducing NSCs, etc.…”

Olfactory mucosa: a rich source of cell therapy for central nervous system repair

“…In other clinical trials, OECs were cultured in vitro and transplanted into the injured site of the spinal cord, but limited follow-up of these patients was carried out Mackay-Sim et al, 2008;Rao et al, 2013;Tabakow et al, 2013). There are also other reports about tumor formation after cell transplantation into animals or humans (Johnson et al, 2008;Amariglio et al, 2009;Seminatore et al, 2010). Thus, it raised a question of how to control cell proliferation, survival, migration, and differentiation in the pathological environment after transplantation.…”

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

“…However, experience with C17.2 NSCs in the PNS has not been uniformly positive. Following the implantation of these cells into rat models of crush, transection and graft, high rates of neuroblastoma formation have been encountered [89] . In addition to these concerns, pragmatic difficulties associated with cell harvest have limited their use.…”

“…Co-culture identified formation of new NMJs; muscle transplanted with stem cells experienced less atrophy 7 and 21-d post injury; cells transplanted after 2-wk were unable to provide any protective effect; motor recovery following repair superior in those muscles receiving stem cells Craff et al [76] Rat sciatic + gastrocnemius muscle [86] Rat sciatic transection ( [87] Rabbit facial nerve transection ( [89] Rat sciatic crush, transection, ( [165] Monkey median transection (50 mm gap)…”