Implanted embryonic sensory neurons project axons toward adult auditory brainstem neurons in roller drum and Stoppini co-cultures.

Previously we have shown in vivo the survival, migration and integration of embryonic dorsal root ganglion (DRG) neurons that were grafted into the inner ear and peripheral auditory nervous system. In order to evaluate relevant factors determining integration of sensory neurons further into the central auditory nervous system, complementary in vitro techniques are necessary. The advantages of in vitro systems are that a large number of factors including various grafts and different conditions can be efficiently examined for. Hence, we co-cultured 300 microm thick postnatal rat brainstem slices containing the cochlear nucleus including the central part of the 8th cranial nerve with mouse embryonic DRG neurons. The organotypic co-cultures were either grown on coverslips using the roller drum method described by Gähwiler or on membranes according to the interface method described by Stoppini. Neurons in the cochlear nucleus were labeled with DiI. The results demonstrate that (1) brainstem slices survive for up to 5 weeks in culture, and that (2) co-cultures of embryonic sensory neurons and brainstem show a high degree of neuronal survival, and that (3) survival and axonal outgrowth from the implanted embryonic neurons are dependent on the presence of the brainstem slice rather than on exogenous NGF and that (4) implanted embryonic neurons send axons toward neurons in the cochlear nucleus.

Tissue engineered fetal skin constructs for pediatric burns.

The management of patients with partial thickness (second degree) burns is problematic due to the different treatments needed for varying depths of injury. A report recently published in The Lancet describes a novel treatment for deep second degree burns using a fetal skin construct (FSC). The authors included eight pediatric patients with small second degree burns. They showed that FSCs reduced the need for autografting of deep second degree burns, with little hypertrophy of new skin and no skin contraction. This technology is new and exciting, but in our opinion several issues must be addressed before FSCs can enter the clinical arena. All of the patients were included in the treatment group, and therefore no comparison with conventional skin substitutes was possible. There is no mention of the use of laser Doppler in any initial assessment of patients. The debridement carried out before application of the FSC is not elaborated upon, and the surface areas involved in the study were very small in most cases, which limits the relevance to patients with larger burns. The use of FSCs gives us an additional option in a range of possible treatments for this notoriously difficult-to-treat patient group.

Neural transplantation cannula and microinjector system: experimental and clinical experience. Technical note.

The authors present a simple, reliable, and safe system for performing neural transplantation in the human brain. The device consists of a transplantation cannula and microinjector system that has been specifically designed to reduce implantation-related trauma and to maximize the number of graft deposits per injection. The system was evaluated first in an experimental rat model of Parkinson's disease (PD). Animals in which transplantation with this system had been performed showed excellent graft survival with minimal trauma to the brain. Following this experimental stage, the cannula and microinjector system were used in eight patients with PD enrolled in the Halifax Neural Transplantation Program who received bilateral putaminal transplants of fetal ventral mesencephalic tissue. A total of 16 transplantation operations and 64 trajectories were performed in the eight patients, and there were no intraoperative or perioperative complications. Magnetic resonance imaging studies obtained 24 hours after surgery revealed no evidence of tissue damage or hemorrhage. Transplant survival was confirmed by fluorodopa positron emission tomography scans obtained 6 and 12 months after surgery. As neural transplantation procedures for the treatment of neurological conditions evolve, the ability to deliver viable grafts safely will become critically important. The device presented here has proved to be of value in maximizing the number of graft deposits while minimizing implantation-related trauma to the host brain.

[Transplantation of fetal dopaminergic cells in Parkinson disease]. / Przeszczepianie plodowych komórek dopaminergicznych w chorobie Parkinsona.

Four patients with severe form of Parkinson's disease received transplantation of fetal dopaminergic cells into the caput of the caudate nucleus. The operation was done by an original method using a device designed specially for this purpose. In all cases the duration of the disease was 10 to 15 years, and the predominating signs were tremor, bradykinesia, and markedly pronounced side effects of the treatment (on-off syndrome and involuntary movements). One patients died 5 weeks after the operation. Autopsy demonstrated good survival of the transplanted cells with good integration with the brain of the recipient and traces of positive immunocytochemical reaction for tyrosine hydroxylase. In the other patients a significant clinical improvement was noted after the operation, with reduced intensity of parkinsonian symptomatology, shortening of the duration of the off phase, improved motor ability and reduced intensity of the involuntary movements. The longest follow-up was 24 months.

Stereotactic technique and pathophysiological mechanisms of neurotransplantation in Huntington's chorea.

In Huntington's chorea, embryonal brain tissue (striatum) was implanted in the caudate nucleus bilaterally, using stereotaxy assisted by CT. A special cannula allowed the placement into the brain of 3 or 4 grafts of embryonal tissue along the determined trajectory by one introduction of the cannula. The pathophysiological mechanism of neurotransplantation in Huntington's chorea is to compensate for the degenerated striatal tissue by embryonal striatum, so it is necessary to supply a quantity of embryonal striatal tissue which enables the whole functional integrity. Therefore, we use material from several embryos.