Rat neurosphere cells protect axotomized rat retinal ganglion cells and facilitate their regeneration.
We investigated the ability of a population of rat neural stem and precursor cells derived from rat embryonic spinal cord to protect injured neurons in the rat central nervous system (CNS). The neonatal rat optic pathway was used as a model of CNS injury, whereby retinal ganglion cells (RGCs) were axotomized by lesion of the lateral geniculate nucleus one day after birth. Neural stem and precursor cells derived from expanded neurospheres (NS) were transplanted into the lesion site at the time of injury. Application of Fast Blue tracer dye to the lesion site demonstrated that significant numbers of RGCs survived at 4 and 8 weeks in animals that received a transplant, with an average of 28% survival, though in some individual cases survival was greater than 50%. No RGCs survived in animals that received a lesion alone. Furthermore, labeled RGCs were also observed when Fast Blue was applied to the superior colliculus (SC) at 4 weeks, suggesting that neurosphere cells also facilitated RGC to regenerate to their normal target. Transplanted cells did not migrate or express neural markers after transplantation, and secreted several neurotrophic factors in vitro. We conclude that NS cells can protect injured CNS neurons and promote their regeneration. These effects are not attributable to cell replacement, and may be mediated via secretion of neurotrophic factors. Thus, neuroprotection by stem cell populations may be a more viable approach for treatment of CNS disorders than cell replacement therapy.
Hill
Andrew J
AJ
Department of Cellular and Molecular Neuroscience, Imperial College London, United Kingdom. a.j.hill@reading.ac.uk
Zwart
Isabel
I
Samaranayake
Asanka Nuwan
AN
Al-Allaf
Faisal
F
Girdlestone
John
J
Mehmet
Huseyin
H
Navarrete
Roberto
R
Navarrete
Cristina
C
Jen
Ling-Sun
LS
D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D053595:Embryonic Stem Cells; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology*; D033581:Stem Cell Transplantation