Clonal human (hNT) neuron grafts for stroke therapy: neuropathology in a patient 27 months after implantation

PT Nelson, D Kondziolka, L Wechsler… - The American journal of …, 2002 - Elsevier
PT Nelson, D Kondziolka, L Wechsler, S Goldstein, J Gebel, S DeCesare, EM Elder
The American journal of pathology, 2002Elsevier
Although grafted cells may be promising therapy for stroke, survival of implanted neural cells
in the brains of stroke patients has never been documented. Human NT2N (hNT) neurons
derived from the NTera2 (NT2) teratocarcinoma cell line were shown to remain postmitotic,
retain a neuronal phenotype, survive> 1 year in host rodent brains and ameliorate motor and
cognitive impairments in animal models of ischemic stroke. Here we report the first
postmortem brain findings of a phase I clinical stroke trial patient implanted with human hNT …
Although grafted cells may be promising therapy for stroke, survival of implanted neural cells in the brains of stroke patients has never been documented. Human NT2N (hNT) neurons derived from the NTera2 (NT2) teratocarcinoma cell line were shown to remain postmitotic, retain a neuronal phenotype, survive >1 year in host rodent brains and ameliorate motor and cognitive impairments in animal models of ischemic stroke. Here we report the first postmortem brain findings of a phase I clinical stroke trial patient implanted with human hNT neurons adjacent to a lacunar infarct 27 months after surgery. Neurofilament immunoreactive neurons were identified in the graft site, fluorescent in situ hybridization revealed polyploidy in groups of cells at this site just like polyploid hNT neurons in vitro, and there was no evidence of a neoplasm. These findings indicate that implanted hNT neurons survive for >2 years in the human brain without deleterious effects.
Elsevier