Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior.
Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes.
Tarasenko
Yevgeniya I
YI
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Gao
Junling
J
Nie
Linghui
L
Johnson
Kathia M
KM
Grady
James J
JJ
Hulsebosch
Claire E
CE
McAdoo
David J
DJ
Wu
Ping
P
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D039481:CD11b Antigen; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D057167:Claudins; D005106:Exploratory Behavior / Q000502:physiology; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D014162:Transfection / Q000379:methods; D014183:Transplantation, Heterologous
D039481:CD11b Antigen; D057167:Claudins; C492353:Cldn11 protein, rat; D005904:Glial Fibrillary Acidic Protein; C509295:ITGAM protein, human; D007211:Indoles; D052119:Lysosomal-Associated Membrane Protein 2; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; C007293:DAPI; D002795:Choline O-Acetyltransferase