Fate of pre-differentiated mouse embryonic stem cells transplanted in unilaterally 6-hydroxydopamine lesioned rats: histological characterization of the grafted cells.
We transplanted mouse embryonic stem (ES) cells pre-differentiated on a PA6 feeder cell layer into the striatum of 6-hydroxydopamine hemi-lesioned adult rats and studied the fate of the grafted cells 1 and 5 weeks post-grafting. At both time points, ES cell grafts contained tyrosine hydroxylase positive (TH+) and 5-HT immunoreactive cells. Between 1 and 5 weeks, there was an enlargement of the grafts and an increase in number of TH+ cells although the differences between the two time points were not significant. The mean number of TH+ neurons per striatum was 330 +/- 73 after 1 week and 1220 +/- 400 after 5 weeks. Over the same time period, mean soma profile area of the TH+ neurons increased significantly by 25.2%. Neurites were longer after 5 weeks (by 24.9%), but the difference to 1 week post-grafting was not reliable. The percentage of TH+ somata without neurites increased from 6.7% after 1 week to 38.3% after 5 weeks (not significant). After 5 weeks, two out of fifteen graft recipients had tumors indicating that pre-differentiation of mouse embryonic stem cells using this differentiation protocol is not sufficient to prevent tumor formation.
Thinyane
Keneuoe
K
Department of Clinical Neurophysiology, University Göttingen, 37075 Göttingen, Germany.
Baier
Paul Christian
PC
Schindehütte
Jan
J
Mansouri
Ahmed
A
Paulus
Walter
W
Trenkwalder
Claudia
C
Flügge
Gabriele
G
Fuchs
Eberhard
E
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001932:Brain Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology / Q000601:surgery; D004195:Disease Models, Animal; D006085:Graft Survival / Q000502:physiology*; D008297:Male; D051379:Mice; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000628:therapy*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015415:Biomarkers; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase