Treatment of spinal cord injury by transplantation of fetal neural precursor cells engineered to express BMP inhibitor.
Spontaneous recovery after spinal cord injury is limited. Transplantation of neural precursor cells (NPCs) into lesioned adult rat spinal cord results in only partial functional recovery, and most transplanted cells tend to differentiate predominantly into astrocytes. In order to improve functional recovery after transplantation, it is important that transplanted neural precursor cells appropriately differentiate into cell lineages required for spinal cord regeneration. In order to modulate the fate of transplanted cells, we advocate transplanting gene-modified neural precursor cells. We demonstrate that gene modification to inhibit bone morphogenetic protein (BMP) signaling by noggin expression promoted differentiation of neural precursor cells into neurons and oligodendrocytes, in addition to astrocytes after transplantation. Furthermore, functional recovery of the recipient mice with spinal cord injury was observed when noggin-expressing neural precursor cells were transplanted. These observations suggest that gene-modified neural precursor cells that express molecules involved in cell fate modulation could improve central nervous system (CNS) regeneration.
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0081, Japan.
Takao
T
Setoguchi
Kinichi
K
Nakashima
Takumi
T
Takizawa
Makoto
M
Yanagisawa
Wataru
W
Ochiai
Masaru
M
Okabe
Kazunori
K
Yone
Setsuro
S
Komiya
Tetsuya
T
Taga
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005455:Fluorescent Antibody Technique / Q000379:methods; D005699:Galactosylceramides / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007527:Isoenzymes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D009836:Oligodendroglia / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051905:Smad6 Protein; D051906:Smad7 Protein; D013116:Spinal Cord / Q000166:cytology; D013119:Spinal Cord Injuries / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta; D014404:Tubulin / Q000378:metabolism; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005699:Galactosylceramides; D005904:Glial Fibrillary Acidic Protein; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D049452:Green Fluorescent Proteins; D007527:Isoenzymes; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D012333:RNA, Messenger; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014404:Tubulin; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; C497803:Smad6 protein, mouse; C497807:Smad7 protein, mouse; C462941:beta3 tubulin, mouse; C496557:Gstp1 protein, mouse