Exp Neurobiol 2003; 12(1): 1-10
Published online November 30, -0001
© The Korean Society for Brain and Neural Sciences
Seung U Kim
Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-31-219-4500, FAX: 82-31-216-6381
Existence of multipotent neural stem cells (NSCs) has been known in developing and adult mammalian central nervous system (CNS) tissues. These cells have capacity to grow indefinitely and multipotent potential to differentiate into three major cell types of CNS, neurons, astrocytes and oligodendrocytes. Recently we have generated continuously dividing immortalized cell lines of human NSCs by introduction of oncogenes and these immortalized NSC lines have been used in studies in basic science of neural development, and transplanted into brain of animal models of human neurological diseases to explore possibility of cell replacement therapy or gene therapy in human patients. It is desirable to obtain a large number of selected subpopulation of neurons or glial cells from continuously growing human NSCs by controlling the differentiation steps more rigorously. One way to accomplish this goal is transfer of relevant regulatory genes into the NSC cells. When human NSCs were transduced with a full length coding region of NeuroD, a neurogenic bHLH transcription factor, NSCs differentiated into neurons expressing neurofilament protein and tetrodotoxin-sensitive Na+ currents. When human NSCs were similarly transduced with Olig2 gene, NSCs differentiated into galactocerebroside-positive, O4-positive oligodendrocytes. When human NSCs were implanted into the brain of rat models of Parkinson disease, Huntington disease and stroke, transplanted human NSCs were found to migrate to the lesion side, differentiate into neurons and astrocytes, and restore functional deficits characteristic ofthe neurological diseases.These results demonstrate that intravenously transplanted human NSCs differentiate into various neural cell types and compensate for the lost functions in rats caused by the focal cerebral ischemia. Continuously dividing immortalized cell lines of human NSCs have have emerged as highly effective source of cells for genetic manipulation and gene transfer into the CNS ex vivo and once transplanted into damaged brain they survive well, integrate into host tissues and differentiate into both neurons and glial cells. By introducing relevant regulatory genes into the human NSC cell line, it is now possible to obtain a large number of selected populations of neurons or glial cells from continuously growing human NSCs. Further studies are needed in order to identify the signals for proliferation, differentiation and integration of NSCs and to determine favorable conditions of host brain environment for implanted NSCs to survive, prosper and restore the damaged brain.