Thymidine analogs are transferred from prelabeled donor to host cells in the central nervous system after transplantation: a word of caution

Stem Cells. 2006 Apr;24(4):1121-7. doi: 10.1634/stemcells.2005-0463. Epub 2005 Dec 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Transport, Active
  • Brain / cytology
  • Brain / growth & development
  • Brain / metabolism
  • Bromodeoxyuridine / pharmacokinetics
  • Cell Proliferation
  • Central Nervous System / cytology*
  • Central Nervous System / metabolism*
  • Female
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Pregnancy
  • Rats
  • Rats, Inbred SHR
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation*
  • Thymidine / analogs & derivatives*
  • Thymidine / pharmacokinetics

Substances

  • Bromodeoxyuridine
  • Thymidine