Effects of cool storage on survival and function of intrastriatal ventral mesencephalic grafts

Ongoing clinical trials with fetal tissue transplants in Parkinson's disease would be facilitated by an effective tissue storage technique that would allow for temporal separation of the procurement of the fetal donor tissue and implantation surgery. In order to develop such a method, we grafted rat or human fetal ventral mesencephalic tissue to the dopamine-depleted striatum of rats either directly, or following pregraft refrigeration in a 'hibernation' medium at 4 °C. Rat tissue transplants were found to normalize amphetamine-induced circling behavior at 6 weeks post-transplantation after having been hibernated for either 2 or 5 days. The number of tyrosine hydroxylase immunoreactive neurons in these hibernated grafts did not differ significantly from that found in matched grafts of fresh tissue. Hibernation for 10 days resulted both in an absence of functional effects and in decreases of graft survival down to 10-20% of control values. Volume assessment of fresh and hibernated grafts prepared from human fetal tissue revealed no adverse effects of a 3 day hibernation interval at 3 weeks after transplantation into immunosuppressed rats. The results indicate that hibernation of neural tissue may be a convenient and simple tool, which can help to guarantee tissue availability at the planned time of implantation in patients and facilitate transport and bacteriological examination. Furthermore, the method offers a simple means which permits prolonged exposure of the neural tissue to trophic factors and specific markers prior to grafting in experimental animals.