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Abstract
Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. All stem cells regardless of their source have general properties: they are capable of dividing and renewing themselves for long periods, are unspecialized and can give rise to specialized cell types.
The two broad types of mammalian stem cells are: embryonic and adult stem cells. The most promising are ESCs, which are present in the very early embryo at the stage of the blastocyst, about 1 week after fertilization. They constitute the ICM and are surrounded by the trophoblast. ESCs can be used as a source for study of basic developmental biology, identification of factors involved in regulation of developmental processes and differentiation into certain cells or tissue, and screening for drugs or toxins.
Adult stem cells are sources of multipotent stem cells with the capacity to differentiate into tissue-specific cell types. These cells represent a potential source of autologous cells for transplantation therapies that eliminates immunological complications associated with allogeneic donor cells as well as bypasses ethical concerns associated with ESCs.
Most cell therapy has not provoked much controversy except ESC therapy. After the successful isolation of hESC s in 1998, ethics and policy debates centered on the moral status of the embryo whether the 2- to 4-day-old blastocyst is a person, and whether it should be protected at all costs.
Spinal cord injury (SCI) can put independent living in danger and totally reconfigure the realities of daily life. The type of spinal cord injury, as well as its level and severity, dictates its functional impact and prognosis.
The classification, which has prognostic, therapeutic, and research value, has four components: (1) sensory and motor levels, (2) the completeness of the injury. (3) The American Spinal Injury Association (ASIA) Impairment Scale and (4) the zone of partial preservation for complete injuries.
The biological response to a spinal cord injury is divided into three phases that follow a distinct but somewhat overlapping sequence: acute (seconds to minutes after the injury), secondary (minutes to weeks after the injury), and chronic (months to years after the injury).
Patients with such injury and their families were told ”nothing can be done”. Once the acute phase of SCI is over, the focus of care shifts to rehabilitation and development of strategies to cope with the residual function of the patient. However few options exist to improve a patient’s neurological status, as cells in the CNS had a limited ability to regenerate and glial scar formation occurs. This produces a barrier to axonal growth.
Targets for intervention in SCI aim toward improved function. These targets include: 1) Reduction of edema and free-radical production, 2) Rescue of neural tissue at risk of dying in secondary processes such as abnormally high extracellular glutamate concentrations, 3) Control of inflammation, 4) Rescue of neuronal/glial populations at risk of continued apoptosis, 5) Repair of demyelination and conduction deficits, 6) Promotion of neurite growth through improved extracellular environment, 7) Efforts to bridge the gap with transplantation approaches, 8) Efforts to retrain and relearn motor tasks, 9) Restoration of lost function by electrical stimulation, and 10) Relief of chronic pain syndromes, 11) Cell replacement therapies. The potential use of stem cells, in particular, to promote regeneration and repair of the injured spinal cord is promising.
Unfortunately, despite the presence of endogenous NSCs populations within the adult spinal cord, the extent of oligodendrocyte differentiation from these endogenous precursor cells is not sufficient to promote remyelination after SCI even after infusion of exogenous growth factors. Thus, restoration of the oligodendrocyte population by cell replacement therapy has been considered as a potentially attractive strategy to promote remyelination after SCI or disorders characterized by loss or a deficiency of myelin.
NSCs were initially obtained from the forebrain subventricular zone and also from the hippocampus, spinal cord, striatum, amygdala, grey matter of temporal and frontal cortex, lateral ventricle and optic nerve.
A heterogeneous population of differentiating ES cells were transplanted into a rat spinal cord 9 days after traumatic injury, they were able to survive, migrate (8 mm away from the lesion edge), and differentiate into astrocytes, oligodendrocytes and neurons, allowing a neurological improvement in treated animals, which recovered leg movement, as compared to paralyzed controls.
Transplantation of combined bone marrow stromal cells and olfactory ensheathing cells into the injured sites of rat spinal cord produced improvement.
Administration of human umbilical cord blood (hUCB) cells intravenously resulted in significant improvement in rats with SCI, particularly in those with hUCB cells administered five days post-injury.
The neural progenitor cells administered intravenously migrated to the site of SCI in rats and differentiated into neurons, astrocytes, and oligodendrocytes.