Lecithinized brain-derived neurotrophic factor promotes the differentiation of embryonic stem cells in vitro and in vivo.
The addition of lecithin molecules to brain-derived neurotrophic factor (BDNF) has been reported to markedly enhance its pharmacological effect in vivo. In the current study, we show that lecithinized BDNF (PC-BDNF) has a higher affinity than BDNF for neural precursor cells. Although BDNF only slightly increased the expression of the genes for Mash-1, p35, 68 kDa neurofilament, and TrkB receptor, PC-BDNF caused a significant increase in their expression. PC-BDNF also increased the level of neurofilament protein and dramatically increased TrkB mRNA gene expression, which was followed by a sustained activation of the p42/p44 extracellular-regulated kinases. Finally, transplantation of PC-BDNF-treated cells was more effective than BDNF-treated cells at improving impaired motor function caused by spinal cord injury. These findings showed that PC-BDNF has a better potential than BDNF for promoting neural differentiation, partly due to a higher cellular affinity. Furthermore, PC-BDNF-treated cells could be useful for transplantation therapy for central nervous system injuries.
Kitagawa
Aki
A
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki 216-8512, Japan. akikit@marianna-u.ac.jp
Nakayama
Toshiaki
T
Takenaga
Mitsuko
M
Matsumoto
Kayo
K
Tokura
Yukie
Y
Ohta
Yuki
Y
Ichinohe
Manabu
M
Yamaguchi
Yoko
Y
Suzuki
Noboru
N
Okano
Hideyuki
H
Igarashi
Rie
R
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology*; D016896:Treatment Outcome
D019208:Brain-Derived Neurotrophic Factor; D010713:Phosphatidylcholines