Neural progenitor cell transplantation and imaging in a large animal model.
To evaluate neural stem/progenitor cell (NPC) transplantation therapy in cat models of neurodegenerative diseases, we have isolated, expanded and characterized feline NPCs (fNPCs) from normal fetal cat brain. Feline NPCs responsive to both human epidermal growth factor (hEGF) and human fibroblast growth factor 2 (hFGF2) proliferated as neurospheres, which were able to differentiate to neurons and glial cells. The analysis of growth factors indicated that both hEGF and hFGF2 were required for proliferation of fNPCs. In contrast to the effect on human NPCs, human leukemia inhibitory factor (hLIF) enhanced differentiation of fNPCs. Expanded fNPCs were injected into the brains of normal adult cats. Immunohistochemical analysis showed that the majority of transplanted cells were located adjacent to the injection site and some fNPCs differentiated into neurons. The survival of transplanted fNPCs over time was monitored using non-invasive bioluminescent imaging technology. This study provided the first evidence of allotransplantation of fNPCs into feline CNS. Cats have heterogeneous genetic backgrounds and possess neurological diseases that closely resemble analogous human diseases. The characterization of fNPCs and exploration of non-invasive bioluminescent imaging to track transplanted cells in this study will allow evaluation of NPC transplantation therapy using feline models of human neurological diseases.
Wang
Lei
L
Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5525, United States.
Martin
Douglas R
DR
Baker
Henry J
HJ
Zinn
Kurt R
KR
Kappes
John C
JC
Ding
Haitao
H
Gentry
Atoska S
AS
Harper
Scarlett
S
Snyder
Evan Y
EY
Cox
Nancy R
NR
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000502:physiology / Q000601:surgery; D001927:Brain Diseases / Q000628:therapy; D016380:Brain Tissue Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008164:Luminescent Proteins; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D015415:Biomarkers; D053605:Leukemia Inhibitory Factor; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor