[Intracerebral transplantation of nerve cells and genetically modified cells for disorders of central nervous system, a basic and clinical study].
OBJECTIVE
To study the survival ability of cerebellar cells and genetically modified cells transplanted in the brains of mice and monkeys and whether the transplanted neurons correct and improve the cerebral function disorders.


METHODS
Suspension of cerebellar tissue from 13-day-old C57BL/6 mouse embryos was transplanted into the cerebellum of 3-month-old BALB/c mice with Purkinji cell degeneration. Since one week after the transplantation, six mice were killed every week till the 8(th) week to examine the cerebellar tissue by immunohistochemistry. Genetically modified neuroblastoma cells with tyrosine hydroxylase (TH) gene and substantia nigra cells of naturally aborted 12-week-old human embryo were implanted into the caudatum nucleus of two monkeys with Parkinson's disease caused by injection of 1-methy-4 pheny-1, 2, 3, 6-tetrahydropyridine. After the operation, the monkeys' symptoms were observed. Six months later, the monkeys were killed. The transplanted areas were examined histologically and immunohistochemically. On the basis of the animal experiment, cerebellar tissue suspension of 9 to 12- week-old human embryos was transplanted into the cerebellum of 6 patients with severe cerebral atrophy, and suspension of substantia nigra cells and adrenal medullary cells from naturally aborted human embryos was transplanted into the caudatum nucleus of 5 patients with late Parkinson's disease. Then the patients were followed up to observe the symptoms.


RESULTS
Surviving transplanted embryonic cerebellar cells could be seen in the cerebelli of recipient mice. Differentiation, maturation, and migration into the granular layer of Purkinje cells could be seen. Axons and dendrites grew from the newly generated Purkinje cells. Many mature nerve cells were monoclone antibody staining positive. The myodynamia of monkeys increased and tremor was alleviated, and torsion spasm was remarkably remitted 5 and 7 days after the transplantation respectively. Genetically modified cells with tyrosine hydroxylase gene could be seen and were pale brown with immunohistochemical staining in the cerebral microcapsule of monkeys. Five of the 6 patients with severe cerebellar atrophy and 5 patients with late Parkinson's disease showed improvement of symptoms beginning from 2 weeks after transplantation. The average score of Webster's scale in the patients with Parkinson's disease decreased from 21 to 11. Th3 condition of two patients with cerebellar atrophy and 2 patients with Parkinson's disease continued to improve or remained stable after two years' follow-up. The condition of other patients had worsened.


CONCLUSIONS
The immature embryonic nerve cells and transgenic TH-cells survive in the brain of recipients and have the potential to regenerate neurons and improve the function of central nervous system.
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan 250012, China.
Chengyuan
C
Wu
Yuguang
Y
Liu
Jiangang
J
Wang
Yang
Y
Yang
Yuquan
Y
Jiang
D000293:Adolescent; D000328:Adult; D000818:Animals; D002531:Cerebellum / Q000166:cytology*; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009474:Neurons / Q000637:transplantation*; D010300:Parkinson Disease / Q000628:therapy*