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(American Journal of Pathology. 2002;160:1201-1206.)
© 2002 American Society for Investigative Pathology

Short Communication

Clonal Human (hNT) Neuron Grafts for Stroke Therapy

Neuropathology in a Patient 27 Months after Implantation

Peter T. Nelson*, Douglas Kondziolka{dagger}, Lawrence Wechsler{ddagger}, Steven Goldstein{dagger}, James Gebel{dagger}, Sharon DeCesare{dagger}, Elaine M. Elder{dagger}, Paul J. Zhang*, Alan Jacobs§, Michael McGrogan§, Virginia M.-Y. Lee* and John Q. Trojanowski*

From the Department of Pathology and LaboratoryMedicine,* the Division of Anatomical Pathology, Universityof Pennsylvania, Philadelphia, Pennsylvania; the Departments ofNeurological Surgery{dagger} andNeurology,{ddagger} University of Pittsburgh,Pittsburgh, Pennsylvania; and Layton Bioscience,Incorporated,§ Sunnyvale, California

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.




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