Trophic factor induction of human umbilical cord blood cells in vitro and in vivo.
The mononuclear fraction of human umbilical cord blood (HUCBmnf) is a mixed cell population that multiple research groups have shown contains cells that can express neural proteins. In these studies, we have examined the ability of the HUCBmnf to express neural antigens after in vitro exposure to defined media supplemented with a cocktail of growth and neurotrophic factors. It is our hypothesis that by treating the HUCBmnf with these developmentally-relevant factors, we can expand the population, enhance the expression of neural antigens and increase cell survival upon transplantation. Prior to growth factor treatment in culture, expression of stem cell antigens is greater in the non-adherent HUCBmnf cells compared to the adherent cells (p < 0.05). Furthermore, treatment of the non-adherent cells with growth factors, increases BrdU incorporation, especially after 14 days in vitro (DIV). In HUCBmnf-embryonic mouse striata co-culture, a small number of growth factor treated HUCBmnf cells were able to integrate into the growing neural network and express immature (nestin and TuJ1) and mature (GFAP and MAP2) neural markers. Treated HUCBmnf cells implanted in the subventricular zone predominantly expressed GFAP although some grafted HUCBmnf cells were MAP2 positive. While short-term treatment of HUCBmnf cells with growth and neurotrophic factors enhanced proliferative capacity in vitro and survival of the cells in vivo, the treatment regimen employed was not enough to ensure long-term survival of HUCBmnf-derived neurons necessary for cell replacement therapies for neurodegenerative diseases.
Chen
Ning
N
Center of Excellence for Aging & Brain Repair, Department of Neurosurgery, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA. nchen1@hsc.usf.edu
Kamath
Siddharth
S
Newcomb
Jennifer
J
Hudson
Jennifer
J
Garbuzova-Davis
Svitlana
S
Bickford
Paula
P
Davis-Sanberg
Cyndy
C
Sanberg
Paul
P
Zigova
Tanja
T
Willing
Alison
A
D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D023822:Tissue Engineering / Q000379:methods*
D036341:Intercellular Signaling Peptides and Proteins