Parkinson's disease is a neurodegenenerative disorder
of the brain that leads to shaking (tremors) and difficulty with walking,
movement, and coordination. This disease most often develops after age 50.
Nerve cells use a brain chemical
called dopamine to help control muscle movement. Parkinson's
disease occurs when the nerve cells in the brain that make dopamine are slowly
destroyed. Without dopamine, the nerve cells in that part of the brain cannot
properly send messages. This leads to the loss of muscle function. The damage
gets worse with time.
Current treatments methods gives temporary relief in
relieving the motor symptoms. It includes the use of oral preparations of
dopamine receptor agonists, L-DOPA and in more advanced cases, the use of
apomorphine. L-DOPA can be made to reach the brain through oral intake of the
drug through intestinal absorption, and via surgical electrodes stimulation to
deliver dopamine to sub-thalamic nucleus and globuspallidus. But the present
treatment methods are not without adverse effects that can sometimes be more
debilitating than the disease itself.
Stem Cells and its Potential:
Stem cells have
remarkable potential to develop into many different cell types in the body
during early life and growth. In addition, in many tissues they serve as a sort
of internal repair system, dividing essentially without limit to replenish
other cells as long as the person or animal is still alive. When a stem cell
divides, each new cell has the potential either to remain a stem cell or become
another type of cell with a more specialized function, such as a muscle cell, a
red blood cell, or a brain cell.
Stem cell therapy in Parkinson's disease:
The race to find permanent cure for Parkinson's disease
seems to be on with many exciting and rapid developments taking place in stem
cell based regenerative research. However on a cautious note it remains to be
shown whether stem cell-derived dopamine neurons can efficiently reinnervate
the regions of the brain like the striatum and provide functional recovery in
The transplantation of the human foetal midbrain tissue
in animals and humans has provided knowledge of a number of requirements
for establishing a clinically competitive Stem Cell-based therapy in
Parkinson's disease. The stem cell grafts should:
a regulated release of dopamine and molecular, electrophysiological, and
morphological properties similar to those of substantia nigra neurons(substantianigra lies in the midbrain immediately dorsal to
the cerebral peduncles);
survival of more than 100,000 dopamine neurons per human putamen(round
structure located at the base of the forebrain);
Re-establish the dopamine network within the striatum and restore the
functional connectivity with host extra-striatal neural circuitries;
the motor deficits resembling human symptoms in animal models of Parkinson's
disease and induce long-lasting andmajor symptomatic relief in patients;
no adverse-effects such as tumor formation, immune reactions and gastric
Another source of stem cells is adult fibroblasts that
are reprogrammed to so called induced pluripotent (capable of differentiating
into one of many cell types) stem cells (iPSCs), and then differentiated to
Recently, dopaminergic neurons were also produced
from iPSCs derived from fibroblasts in adult humans and Parkinson's disease
patients. Such neurons survived transplantation into the striatum of
Parkinson's disease rodents and produced some degree of functional recovery.
Fetal brain neural stem cells (NSC)-derived
are associated with lower risk of tumor formation and
immune rejection than ESCs. Early studies reported that non-differentiated NSCs
taken from a human source and transplanted in rats have limited differentiation
and only partially affect PD-like symptoms. A more recent
study showed that non-differentiated NSCs implanted into Parkinson's primates
survived, migrated, and had a functional impact.
A small number of NSC
progeny differentiated into Dopamine phenotypes.
Bone marrow-derived stromal cells and mesenchymal stem
cells (MSCs) have beenproposed as potential cell sources for transplantation in
It has beenreported that non-differentiated murine (a medical
laboratory animal) MSCs are able to differentiate into
tyrosinehydroxylase-positive neurons and improve motor performance in mice.
Also, it has been demonstrated that cells with Dopaminergic properties can be
produced from bothrat and human mesenchymal stem cells
thattransplantation of these cells gave rise to improvement of motor function
in an animal model of Parkinson's.
Although the ability to restore function in Parkinson's
patients by dopaminergic neuron replacement has been demonstrated to some
extent with hfVM tissue, the focus is now on producing standardized
dopaminergic neuroblasts from stem cells for transplantation.
iPSCs seem the simplest to manipulate towards a dopaminergic fate and to
produce large numbers of dopaminergic neurons in vitro, but fetal brain NSCs
could also be useful for clinical application. Both iPSC-derived and directly
converted dopaminergicneurons have one more advantage as they potentially can
be used for autologous transplantation in Parkinson's patients.
Several important properties will be decisive for the
success or failure of a clinical trial in Parkinson's in humans.
include the ability of the Stem Cell-derived dopaminergic neurons to
substantially re-innervate striatum, restore dopamine release and markedly
improve Parkinson's symptoms. Before human trials using the method of
transplantation of stem cell-derived dopaminergic neurons are started exclusion
of the risks for tumor formation, immune reactions, and development of
gastro-intestinal disorders need to be proven. However this major research
effort is not too far in the distant future and the current evidence will help
in the development of a clinically competitive stem cell-based therapy. If this
happens it will opens up the possibility for an effective restorative treatment
for Parkinson's patients.
Reference: Clinical application of stem cell therapy in Parkinson's disease; Marios
et al; BMC Medicine 2012.