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Abstract
Just a decade ago, neuroscience textbooks held that neurons in the adult human brain and spinal cord could not regenerate. Once dead, it was thought, central nervous system neurons were gone for good. Because rebuilding nervous tissue seemed out of the question, research focused almost entirely on therapeutic approaches to limiting further damage.
Replacing the worn out or injured cells by functional cells to restore the normal function of the tissues or organs is the underlying principle of cell replacement therapy, otherwise also called as regenerative medicine. It is hoped that the organs or tissues treated by this approach can perform their normal function more efficiently than the ones treated by conventional therapies like transplantation and pharmocological therapy.
Stem cells are cells in the body that can develop into any of the different cell types needed to make a human being. They are immature cells characterized by prolonged cell renewal capacity through cell division, and the ability to differeلntiate into multiple cell types, depending on their origin, under certain physiological or experimental conditions.
Transplantation of stem cells or their derivatives, and mobilization of endogenous stem cells within the adult brain, have been proposed as future therapies for neurodegenerative diseases. It may seem unrealistic, though, to induce functional recovery by replacing cells lost through disease, considering the complexity of human brain structure and function. Studies in animal models have nevertheless demonstrated that neuronal replacement and partial reconstruction of damaged neuronal circuitry is possible. There is also evidence from clinical trials that cell replacement in the diseased human brain can lead to symptomatic relief.
The main pathology in Parkinson’s disease is a degeneration of nigrostriatal dopaminergic neurons. Studies in patients with Parkinson’s disease after intrastriatal transplantation of human fetal mesencephalic tissue, rich in postmitotic dopaminergic neurons, have provided proof of principle that neuronal replacement can work in the human brain.
In its common form, amyotrophic lateral sclerosis is characterized by progressive dysfunction and degeneration of motor neurons in cerebral cortex, brain stem and spinal cord. To have long-term value, stem cell therapy must restore function of both upper and lower motor neurons. Successful replacement of cortical motor neurons requires not only re-establishment of spinal cord connections but also precise functional integration of the new neurons into cortical circuitries.
Huntington’s disease is an autosomal dominant neurodegenerative disorder associated with progressive cell loss and atrophy predominantly in the striatum and neocortex, Cell therapy in Huntington’s disease aims at restoring brain function by replacing these neurons.
Compared with neurodegenerative disease, stroke possesses special conditions that impact the potential success of transplantation to enhance neurological recovery including; the anatomy, time of the stroke, the vascular supply, site of implantation and type of patients enrolled in clinical trials.
Another disease of interest is Multiple sclerosis which presents particular and serious problems to those attempting to develop cell-based therapies, as the occurrence of innumerable lesions scattered throughout the central nervous system, axon loss, astrocytosis, and a continuing inflammatory process. Nevertheless, the limited and relatively focused nature of damage to oligodendrocytes and myelin, at least in early disease, the large body of available knowledge concerning the biology of oligodendrocytes, and the success of experimental myelin repair, have allowed cautious optimism that therapies may be possible.
Also, there have been several different experimental approaches to cell therapy for Muscular dystrophies which are a heterogeneous group of inherited disorders clinically manifested by progressive muscle weakness and wasting and, in some cases, death. Although much of the molecular genetics of muscular dystrophies have been elucidated, there is still no effective cure for any of them.
Moreover basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuities by either regeneration or neuronal/glial replacement.
But in spite that stem cell therapy seems to be promising in a multiple neurological disorders, many technical obstacles must be overcome and unanswered questions resolved before stem cells can safely fulfill their promise.