Neural transplantation of human neuroteratocarcinoma (hNT) neurons into ischemic rats. A quantitative dose-response analysis of cell survival and behavioral recovery

Transplantation of fetal neuronal tissue has been used successfully to amel iorate symptoms of neurodegenerative disease in animals and humans. This te chnique has recently been extended as an experimental treatment for ischemi c brain damage. However, due to ethical issues with the use of fetal cells for the treatment of any human disease, there has been a concerted effort t o find alternative graft sources for neural transplantation. The human neur oteratocarcinoma neuron cell is derived from an embryonal teratocarcinoma c ell line that can be differentiated into post-mitotic neurons. Neural trans plantation of human neuroteratocarcinoma neurons has recently been shown to produce behavioral amelioration of symptoms in rats with ischemia-induced injury. The present study was undertaken to: (i) determine the minimum effe ctive number of transplanted human neuroreratocarcinoma neurons required fo r amelioration of ischemia-induced behavioral dysfunction; and (ii) quantif y the survival of human neuroteratocarcinoma neurons in vivo. Transplants o f 0, 5, 10, 20, 40, 80 or 160 x 10(3) human neuroteratocarcinoma neurons we re made into rats that sustained ischemic damage. Animals that received 40, 80 or 160 x 10(3) human neuroteratocarcinoma neurons demonstrated a dose-d ependent improvement in performance of both the passive avoidance and eleva ted body swing tests. At the conclusion of behavioral testing, human neurot eratocarcinoma neurons were identified in paraffin sections with human neur al cell adhesion molecule MOC-1 and human neurofilament antibodies. Transpl ants of 80 or 160 x 10(3) human neuroteratocarcinoma neurons demonstrated a 12-15% survival of human neuroteratocarcinoma neurons in the graft, while transplants of 40 x 10(3) human neuroteratocarcinoma neurons demonstrated a 5% survival. Transplantation of human neuroteratocarcinoma neurons ameliorated behaviora l deficits produced by ischemic damage. The human neuroteratocarcinoma neur on, additionally, showed greater survival than that reported for fetal cell s when transplanted into the brain. Therefore, this readily available cell may prove to be an excellent candidate for the treatment of ischemic damage in human patients. (C) 1999 IBRO, Published by Elsevier Science Ltd.