Biomedical Engineering Reference
In-Depth Information
overgrowth, but rather by uneven and patchy reinnervation or by chronic
inflammatory and immune responses around the graft. Only 5-10% of fetal mesen-
cephalic grafts are dopaminergic neurons. It is not yet known whether it is favor-
able to implant a pure population of dopaminergic neurons or whether the graft
should also contain a specific composition of other neuron types and glial cells to
induce maximum symptomatic relief.
Fetal tissue transplantation has been performed in 350 patients, including trials
using pig fetal tissue. So far, the success of reversing Parkinson's disease using fetal
tissue has been limited at best. However, in the most successful cases, patients have
been able to lead an independent life without L-dopa treatment (
http://www.parkinson.
org/site/pp.asp?c=9dJFJLPwB&b=71125
)
. The limitations include (a) lack of
sufficient tissue for the number of patients in need, (b) variation in results between
patients ranging from no benefit to reversal of symptoms, and (c) Occurrence of
uncontrolled flailing movements (called dyskinesias).
The many criteria for the cells used in therapy include the ability to produce
dopamine, to divide and survive in the brain, and to integrate into the host brain.
For these reasons, differentiated embryonic stem cells offer more promise. Mouse
ES cells have been used in rat models of Parkinson's disease and recently human
ES cells have been reported to differentiate into dopamine-producing neurons in
culture [
56,
57
] .
Another consideration is the immune problem. It was believed that the brain is
an immunologically privileged site tolerating transplanted cells from a different
individual (meaning that the immune system will not attack tissue transplanted into
this location). However, a recent report challenges this view (
http://stemcells.nih.
gov/info/scireport/chapter8.asp
)
[
54
]. For this reason autologous cells may offer a
safer alternative. Neural stem cells and HSC are both likely candidates [
54
] . Also,
dental pulp cells in both rats and humans produce neurotrophic factors and are a
candidate for autologous transplantation in Parkinson's [
58
] .
If the adult stem cell treatment cannot help as the regenerative approach to PD,
maybe we shall have to use embryonic stem cell (ESC). Somatic cell nuclear trans-
fer was used to clone Dolly, the sheep. Since then, seven animal species have been
cloned using this technique. A modified version for use in human's ES is as follows:
The patient's DNA is injected into an enucleated unfertilized egg and used to gener-
ate ES cells which are then cultured and allowed to differentiate, followed by trans-
plantation into the patient. This technique is called therapeutic cloning. The use of
such cells may bypass the ethical objections and immunological issues of using ES
cells and is the future of stem-cell clinical application.
Nevertheless, very recently the encouraging results have been published on the
use of adult stem cells in one patient suffering PD, which caused improvement in
entire clinical picture and put the perspective of this kind of treatment into the
scope of regenerative stem cell medicine. UCLA researchers published their
results in February issue of the
Bentham Open Stem Cell Journal
which outlines
the long-term results of the trial (Dr. Michel Levesque). They have documented
the first successful adult neural stem cell transplantation to reverse the effects of
