introduction
Major Characteristics
Stem cell transplantation
NCL (Batten disease)
Treatment guide
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The Neurosurgery Department of Navy general hospital welcome you!
Stem cell transplantation (SCT )
Neural stem cells (NSCs) are a kind of special cells possessing self-renewal
and multi-directional differentiation potential. Under special condition,
it can proliferate and differentiate to special direction (such as neuron).This
makes it possible that the substitution treatment of neural stem cell
in CNS injury disease and degenerative neural disorders. Recent research
shows that this treatment make a good progress in the treatment of Parkinson’s
disease, residual of cerebral infarction, cerebral atrophy, NCL and
encephalodysplasia. It is currently being proposed and need to be proved
as soon as possible. A clinical trial (Phase I) to test the safety and
efficacy of this therapy is in progress by Stem Cells Inc in University
of Connell in the USA.
Based on our laboratory preliminary data, the fetal neural stem cell
derived from 11 weeks embryo, can stably amplification under EGF, bFGF
existing, and have the capability of differentiate to neuron, astrocyte
and oligodendrocyte[1]. The results of research can proved that NSC
which be transplanted to nervous damage spot, can differentiate and
replace the damaged cells and rebuilt the nervous cycle, and product
the neural nutrition factor, neural protect factor, and thus inhibit
the degeneration of nervous or promote the regeneration of nervous.
This approach delivers cells that can make a correct version of the
faulty protein to the brain. These cells might replace cells that die
during the disease process.
Whether CNS exists rejection reaction to neural stem cell transplantation
is another question puzzling the clinical usage. Many authors think
that existing of blood-brain barrier (BBB) and lymphatic system deficiency
in brain play an important role for the survival of grafts. Another
cause is the neural stem cell do not easily destroyed because of being
lack of immunogenicity. We believe embryo NSC may be an ideal graft
for transplantation therapy, can be used in the treatment for neurodegeneration
diseases.
The approaches to transplantation in researches are reported include
direct transplantation into brain tissue using stereostactic techniques,
indirect transplantation into brain via the venous, subarachnoid cavity
or ventricle. We think the advantage of stereostactic operation is not
through the BBB, and the neural cell have ability to migrate and involve
in the rebuilt of function zone. While it has been suggested that transplanted
cells have considerable ability to migrate as needed, there may be advantages
in placing the cells at or near the injury. We think the operation is
safe. As timing of transplantation, maybe only in the early stage the
transplantation will be effect and halt the progress of the disease.
The patients undergone the transplantation showed the improvement of
symptom one week after transplantation, we think the early result may
be related with the transplanted NSC secreting some growth factor and
priming the repair progress of host, and long-term result depend on
the rebuilt of nervous cycle and formation of synapse. The release of
neurotransmitter in transplanted cells also promotes the recovery of
nervous function. But the long-term result need to follow-up and further
investigation.
A deeper understanding of these interactions may greatly improve neural
stem cell transplantation treatment to CNS lesions, such as NCL, CA.
Neuronal Ceroid Lipofuscinoses (NCL)
Neuronal Ceroid Lipofuscinoses (NCL) are a group of recessively inherited
encephalopathies that together form the most prevalent neurodegenerative
diseases of childhood, and it happen on adults. Another name is Batten
disease; it can be character as INCL, CLN2-4 subgroup. The patient is
usually dominant heredity, at some time by recessive heredity. The major
clinical symptoms of NCL include rapid deterioration of vision, seizures,
cognitive, neuromotor dysfunction, and dementia. The hallmark of neuropathology
is character as lipopigments deposit in the intracellular of the cerebral
cortex and cerebellum. Ultrastructural findings in neural and non-neural
tissues are consistent with granular osmiophilic deposits (GROD). The
intracellular accumulation of autofluorescent lipopigments is characteristic
of NCL. It can be seen in epithelial cell of skin eccrine sweat glands
and blood lymphocyte.Nowadays there are no special treatments for Batten
disease. The development of therapy for Batten disease is at a very
early stage but is progressing. The ultimate aim is a complete cure
for all types of Batten disease. The promising methods include enzyme
repairmen, immune therapy gene therapy and stem cell therapy. A medicine
named as Cystagon character as nutrients of lysosome in the treatment
of cystinosis, can decrease the lipofuscin deposits in lymphocyte of
NCL patients, which will make it possible to control NCL progress. The
immune system seems to be affected, especially in juvenile NCL. A trial
to suppress the immune system in patients is underway. Because of the
deficit of genes, it is a way to deliver a corrected copy of the faulty
gene into the cells that need it to function efficiently and correctly.
It is most likely to be effective for NCLs caused by mutation in genes.
Nowadays there are no special treatments for NCL. The current treatment
method includes gene therapy, stem cell transplant and Immune therapy.
Embryo neural stem cells were implanted into basal nuclei with stereotactic
operation in 3 cases of NCL patients from June. 2005 to Dec. 2006. All
patients who received transplants benefited from the SCT (stem cell
transplantation) operation, without serious complication. The neurological
statue of three patients (with age ranging 6-8 years, mean 7) was improved
in one month after operation. One year after SCT, the PET in one patient
showed the significance increase of metabolism in brain cortical. So
we think SCT currently can be recommended as therapy for NCL. But the
long term effectiveness should be further observed.
Cerebellar atrophy (CA)
The stem cells were implanted into CA dentate nuclei with stereo tactic
operation in 21 CA patients (8 male and 13 female with age ranging 19-71,
mean 46) from Feb. 2000 to Aug. 2003. The effective rates were 61.9%.
3 months after transplantation, 85.7% 6 months after transplantation,
and 90. 4% during a follow-up of 12-28 months (mean 18 months). It is
feasible and effective to implant the neural stem cells expanded in
vitro for treatment of CA.
E-mail:centre@navy-neurosurgery.com
Mailing Address:
Department of Neurosurgery
General Navy Hospital of PLA
6 Fucheng Road, Beijing 100037, P.R. China
Tel: （010）66958514
Fax: （010）68780358
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