Isolation, Characterization, and use of Stem Cells from the CNS

Abstract

The nervous system of adult mammals, unlike the rest of the organs in the body, has been considered unique in its apparent inability to replace neurons following injury. However, in certain regions of the brain, neurogenesis occurs postnatally and continues through adulthood. The nature, fate, and longevity of cells undergoing proliferation within the CNS are unknown. These cells are increasingly becoming the focus of intense scrutiny; this is a recent development that has led to considerable controversy over the appropriate terminology to describe neural cells as they pass through different stages of proliferation, migration, and differentiation. Continuing studies detailing the properties of mitotic populations in the adult CNS will provide a better understanding of the nature of these cells during their development and should lead to a more consistent nomenclature. Studies of neural precursors isolated from the embryonic brain have indicated that many subgroups of cells undergo mitosis and subsequent differentiation into neurons and glia in vitro. A number of substances, such as growth factors and substrate molecules, are essential for these processes and also for lineage restriction and fate determination of these cells. Recent studies have shown that cells with proliferative capabilities can also be isolated from the adult brain. The nature of these cells is unknown, but there is evidence that both multipotent cells (stem cells) and lineage-restricted cells (neuroblasts or glioblasts) are resident within the mature CNS and that they can be maintained and induced to divide and differentiate in response to many of the same factors that influence their embryonic counterparts. Presently, it is unclear how many potentially quiescent precursor cells exist in the adult brain or what combination of growth factors and substrate molecules is involved in the proliferation and differentiation of these cells. Some of these questions are currently being addressed by using immortalized neural precursors or growth factor-expanded populations of primary precursors to model precursor responsiveness to environmental manipulations. Because in vitro culture conditions are unlikely to provide all of the factors necessary for inducing the proliferation and differentiation of neural precursors, recent studies have explored the properties of well-characterized precursor populations after implantation back into specific regions of the developing or adult CNS. These studies have highlighted the importance of the microenvironment in precursor differentiation and further suggested that precursor plasticity is a characteristic that is probably common to neural precursors throughout the CNS.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain protection using autologous bone marrow cell, metalloproteinase inhibitors, and metabolic treatment in cerebral ischemia

“…Woodbury et al (35) suggested that BMCs can differentiate into neural phenotypes in vitro. BMCs are likely to retain the capacity to respond to local epigenetic signals and to differentiate with a terminal phenotype appropriate for that ectopic site in the ischemic brain that represents a different environment than the intact CNS (11,36). Together, injected BMCs survived and were likely to differentiate into at least a modest number of neuronal and glial cell phenotypes in lesions, although it remains unclear how much they contributed to the behavioral rescue and improvement.…”

“Global” cell replacement is feasible via neural stem cell transplantation: Evidence from the dysmyelinated shiverer mouse brain

“…The NSCs differentiate into neurons in regions undergoing neurogenesis or into glia, where gliogenesis is ongoing (6,24,25). Therefore, they emulate endogenous NSCs as well as NSC clones propagated by a variety of techniques from other structures (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). After 0-2 mitoses in the first 48 hr posttransplant, they become quiescent and intermingle nondisruptively with endogenous progenitors.…”

“…The recognition that NSCs, propagated in culture, could be reimplanted into mammalian brain, where they could reintegrate appropriately and stably express foreign genes (1)(2)(3)(4)(5)(6)(7)(8)(9), provided hope that their use might make feasible a variety of novel therapeutic strategies. When exogenous NSCs are transplanted into germinal zones, they circumvent the blood-brain barrier, migrate to distant CNS regions, and participate in the normal development of multiple regions throughout the brain and at multiple stages (from fetus to adult), integrating seamlessly within the parenchyma, differentiating appropriately into diverse neuronal and glial cell types.…”

Hematopoietic potential of stem cells isolated from murine skeletal muscle

“…egenerative stem cells can be found in many adult tissues (1)(2)(3)(4)(5)(6). Although possessing substantial capacity to proliferate and differentiate, such cells are thought to be committed to differentiate exclusively into the tissues in which they reside.…”