| The field of stem cells for application in the area of regenerative medicine is an expanding area of investigation that holds promises for the development of novel therapies for heretofore-incurable disorders. Neurodegenerative disesases and, more generally, disorders of the central nervous system (CNS), represent the most important sectors of application for cell-replacement and stem cell-based therapies.
A renewable source of normal neural cells would significantly reduce the need for foetal tissue in therapeutic approaches aimed at restoring neurological function by intracerebral transplantation of precursor cells 1. Implantation of neural cells has been tested in various animal models of neurological disorders including
i) metabolic deficit 2;
ii) Huntington's disease 3;
iii) spinal cord injuries 4,5 , and
iv) experimental paradigms of demyelinating diseases 6,7. The first of these treatments to reach the clinical stage was transplantation for Parkinson's disease 8, with some patients experiencing both dramatic improvement in motor functions and decreased dependence on L-dopa and other showing no apreciable benefits 8.
A major obstacle to the progression of neural transplantation from the experimental level to the clinic is the source of donor material 9. In addition to the significant moral and ethical issues surrounding the procurement of foetal tissue, other parameters such as age, storage, viability and contamination must be standardized, making elective surgery difficult to schedule 10. To further compound the problem, multiple foetuses are usually required for a single transplant thereby introducing heterogeneity in the donor tissue and increasing the probability of immunological rejection or contamination 9. An awareness of these difficulties has driven the search for alternative donor sources. Thus, immortalized brain precursors 11,12, xenogeneic tissue 13,14, or genetically engineered cells 15 have been used in experimental neural transplantation while, more recently, autologus transplantation of dopamine-producing cells from the carotid body has produced significant functional recovery in parkinsonian rats 16
The isolation of putative stem cells from the embryonic 16 and adult rodent CNS 17-21 has been recently accomplished by means of growth factor stimulation. Since CNS stem cells have an extended self-renewal capacity and possess the potential to give rise to all three major brain cell types 19,22, virtually unlimited numbers of neurons, astrocytes and oligodendrocytes could be generated under standardized conditions.
In this paper, I shall be highlighting, how neural stem cells (NSCs) can be isolated from the brain, including the human CNS, can be propagated for well over two years, are cryopreservable, and differentiate spontaneously into neurons, astrocytes and oligodendrocytes when growth factors are removed 1,23. NSCs are functionally stable, retain a steady growth profile, their multipotency, and an unchanged capacity for neuronal differentiation and do not show any sign of transformation over time 24,25. When grafted into the CNS of adult rodents NSCs'progeny survive, migrate, and differentiate into neurons and glia 23 ( Figure 1). Tumor formation is never observed, even in immunodeficient hosts. Most important, I shall be illustrating preliminary, yet very solid evidence on the capacity of NSCs to improve behavioral anormalities when transplanted in experimental models of neurodegenerative disorders. This shows that somatic (i.e.) tissue specific stem cells of the brain can function as an effective therapeutic tool for the cure of CNS disorders. |
| References
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