Previous research has demonstrated that the replacement of neurons in the mammalian CNS, lost to trauma or neurodegenerative disease, requires fetal tissues to be utilized. While this approach has been successful in the treatment of Parkinson's disease and has applied to Huntington's disease, and spinal cord injury, the ethical and logistical issues involved in obtaining enough donor tissue of appropriate age and region make the widespread therapeutic use of this transplantation strategy extremely limited. As such, many laboratories have investigated alternative tissues and/or cells for use in transplantation experiments to replace CNS neurons. Immortality is established when a cell loses its cell cycle checkpoint pathways. The overriding of natural cellular senescence takes place when the inactivation of p53/p16/pRb occurs during immortalization protocols. The mechanism controlling cellular senescence and immortalization was described as a two-stage mechanism, according to which, telomerase activity is a key factor in the establishment of immortality.
Immortalized neural cell lines have provided novel and important insight into fundamental principles of developmental neurobiology. These cell lines maintain the capacity to differentiate into neurons, astrocytes, and oligodendrocytes despite continued passage in cell culture, a property that is evidenced both in vitro and in vivo. Many of these cell lines differentiate after engraftment into the CNS with morphological and functional properties indistinguishable from endogenous neurons and glia.
|Tissue source||Cell line||Immortalizing protein||Cell lineage in vitro|
|E14 mouse hypothalamus||Ht9-C7||T-ag||primitive neurosecretory cell|
|E7 quail neuroretina||QNR/D||ts-RSV||amacrine/ganglion cell (GABA)|
|P2 rat cerebellum||ST15E, M15B||ts-T-ag, neu||astrocyte/neuron|
|E10 mouse mesencephalon||2.3D, NZen5-NZen37||c-myc, N-myc||neuroepithelial precursor astrocyte/neuron|
|Pl mouse olfactory bulb||OLB13-OLB24||avian myc||neuron/oligodendrocyte|
|P4 mouse cerebellum||C17.2, C27-3||avian myc||neuron/oligodendrocyte astrocyte / neuron / oligodendrocyte|
|Pl mouse striatum||SVLT.3.8||T-ag||astrocyte/neuron|
|E16 rat hippocampus||HiB5||ts-T-ag||neuroepithelial precursor|
|E17 rat hippocampus||H19-7, WH19-4||ts-T-ag||astrocyte/neuron|
|E13 rat medullary raphe||RN33B||ts-T-ag||neuron (glutamate)|
|E14 rat striatum||M213-20, M26-1F||ts-T-ag||neuron (GABA)|
|E7 mouse hippocampus||MK31||ts-T-ag||neuron|
|El8 rat hippocampus||HMR10-3||ts-T-ag||neuron|
|El3 rat medullary raphe||RN46A||ts-T-ag||neuron (serotonin)|
|P5 mouse cerebellum||GC-B6||ts-T-ag||astrocyte/neuron|
|E14 rat striatum||ST14A||ts-T-ag||neuroepithelial precursor|
|E12 rat mesencephalon||IRB3 A-N27||ts-T-ag||astrocyte/neuron (dopamine)|
|E14 rat mesencephalon||CSM14.1.4||ts-T-ag||astrocyte/neuron (dopamine)|
|Adult rat neuronal precursor cells||HC2S2||v-myc||neuron|
|E14 mouse hippocampus||MHP36||ts-T-ag||astrocyte/neuron|
|13-week human whole brain||B4, C2, CIO, JA3||v-myc||neuron astrocyte/neuron|
|15-week human telencephalon||H6||v-myc||astrocyte/neuron/oligodendrocyte|
Table.1 Immortalized CNS neural cells lines.
Chronic neuropathic pain is a severe complication for much spinal cord injury (SCI) patients and the descending serotonergic system has been implicated in modulating nociceptive input. Using a model of chronic neuropathic pain in which the sciatic nerve is unilaterally constricted. Eaton and co-workers transplanted RN46A cells that had been genetically engineered to secrete BDNF into the intrathecal space of the lumbar spinal cord. BDNF expression in RN46A cells potentiates both their survival and serotonergic phenotype in vivo. Following these grafts, there was a reduction in tactile and cold allodynia as well as thermal hyperalgesia. The effects of these grafts could be blocked with the serotonergic antagonist methysergide, demonstrating that the effects were mediated by the released serotonin.
Immortalized neural precursor cell lines have proven effective in other models of CNS repair. The shiverer mouse suffers from widespread CNS demyelination because of dysfunctional oligodendrocytes. The meander tail mouse is characterized by a loss of cerebellar granule neurons. Synder and colleagues have examined the potential of engrafted C17.2 cells to repair these respective deficits. Following engraftment of C17.2 cells into the postnatal day 1 shiverer mouse ventricle, these cells myelinated roughly 50% of CNS axons, an extent of myelination that decreased tremor and restored near-normal motor function.
Immortalized cell lines have become popular neuroscience research tools because of all the characteristics we mentioned above. As an industry-leading neuroscience research services provider, Creative Biolabs has been focusing on the application of immortalized cell lines in neuro over years. We are confident in offering quality-assured neuro-based immortalized cell lines custom productions. If you are looking for neuro-based immortalized cell lines custom productions or have any other inquiries about neuroscience research, please don't hesitate to contact us for more information.
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