Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation.
It is now well accepted that the brain is able to generate newborn neurons from a population of resident multipotential neural stem cells (NSCs) located in two discrete regions of the brain. The capacity for neurogenesis appears to diminish over the lifespan of an organism. Methods to potentiate the proliferation of new neuronal or glial cells within the central nervous system from resident NSCs could have therapeutic potential following an insult, such as stroke, or to replace lost cells as a result of a neurodegenerative disease. We implanted cells from a human NSC cell line, CTX0E03, originally derived from fetal cortical tissue directly into the ventricles of aged rats. CTX0E03 cells have angiogenic properties via secretion of growth factors, so we investigated if the implanted cells would stimulate proliferation of NSCs within the subgranular zone (SGZ) of the dentate gyrus. Bromodeoxyuridine staining demonstrated significantly increased proliferation in the SGZ. Absence of double labeling for human nuclear antigen suggested that the increased proliferation was from endogenous neural progenitor cells. The acute treatment also led to an increased number of immature neurons as demonstrated by immunohistochemical staining for the immature neuronal marker doublecortin. The data suggest that implants of exogenous NSCs may promote regeneration in aging organisms through stimulation of endogenous neurogenesis.
Park
Dong-Hyuk
DH
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida 33612, USA.
Eve
David J
DJ
Sanberg
Paul R
PR
Musso
James
J
Bachstetter
Adam D
AD
Wolfson
Alan
A
Schlunk
Andrea
A
Baradez
Marc-Olivier
MO
Sinden
John D
JD
Gemma
Carmelina
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000166:cytology* / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014183:Transplantation, Heterologous
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine