Thymidine analogs are transferred from prelabeled donor to host cells in the central nervous system after transplantation: a word of caution.
Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine, iododeoxyuridine, and tritiated thymidine, label dividing cells by incorporating into DNA during S phase of cell division and are widely employed to identify cells transplanted into the central nervous system. However, the potential for transfer of thymidine analogs from grafted cells to dividing host cells has not been thoroughly tested. We here demonstrate that graft-derived thymidine analogs can become incorporated into host neural precursors and glia. Large numbers of labeled neurons and glia were found 3-12 weeks after transplantation of thymidine analog-labeled live stem cells, suggesting differentiation of grafted cells. Remarkably, however, similar results were obtained after transplantation of dead cells or labeled fibroblasts. Our findings reveal for the first time that thymidine analog labeling may not be a reliable means of identifying transplanted cells, particularly in highly proliferative environments such as the developing, neurogenic, or injured brain.
Burns
Terry C
TC
Stem Cell Institute, University of Minnesota, 420 Delaware Street, Minneapolis, Minnesota 55455, USA.
Ortiz-González
Xilma R
XR
Gutiérrez-Pérez
María
M
Keene
C Dirk
CD
Sharda
Rohit
R
Demorest
Zachary L
ZL
Jiang
Yuehua
Y
Nelson-Holte
Molly
M
Soriano
Mario
M
Nakagawa
Yasushi
Y
Luquin
María Rosario
MR
Garcia-Verdugo
Jose Manuel
JM
Prósper
Felipe
F
Low
Walter C
WC
Verfaillie
Catherine M
CM
D000818:Animals; D000831:Animals, Newborn; D001693:Biological Transport, Active; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013936:Thymidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D001973:Bromodeoxyuridine; D013936:Thymidine