Neural cell adhesion molecule L1-transfected embryonic stem cells promote functional recovery after excitotoxic lesion of the mouse striatum.
We have generated a murine embryonic stem cell line constitutively expressing L1 at all stages of neural differentiation to investigate the effects of L1 overexpression on stem cell proliferation, migration, differentiation, cell death, and ability to influence drug-induced rotation behavior in an animal model of Huntington's disease. L1-transfected cells showed decreased cell proliferation in vitro, enhanced neuronal differentiation in vitro and in vivo, and decreased astrocytic differentiation in vivo without influencing cell death compared with nontransfected cells. L1 overexpression also resulted in an increased yield of GABAergic neurons and enhanced migration of embryonic stem cell-derived neural precursor cells into the lesioned striatum. Mice grafted with L1-transfected cells showed recovery in rotation behavior 1 and 4 weeks, but not 8 weeks, after transplantation compared with mice that had received nontransfected cells, thus demonstrating for the first time that a recognition molecule is capable of improving functional recovery during the initial phase in a syngeneic transplantation paradigm.
Bernreuther
Christian
C
Zentrum für Molekulare Neurobiologie Hamburg, University of Hamburg, D-20251 Hamburg, Germany.
Dihné
Marcel
M
Johann
Verena
V
Schiefer
Johannes
J
Cui
Yifang
Y
Hargus
Gunnar
G
Schmid
Janinne Sylvie
JS
Xu
Jinchong
J
Kosinski
Christoph M
CM
Schachner
Melitta
M
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000473:pathology* / Q000601:surgery; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D004311:Double-Blind Method; D004622:Embryo, Mammalian; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods
D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D001973:Bromodeoxyuridine