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TISSUE-SPECIFIC STEM CELLS

Thymidine Analogs Are Transferred from Prelabeled Donor to Host Cells in the Central Nervous System After Transplantation: A Word of Caution

^a Stem Cell Institute,
^b Department of Neurosurgery,
^c Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA;
^d Clínica Universitaria, Universidad de Navarra, Pamplona, Spain;
^e Department of Cell Biology, Instituto Cavanilles and Centro de Investigacion Principe Felipe, University of Valencia, Valencia, Spain;
^f Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA;
^g Division of Neurosciences, Centre for Applied Medical Research, Pamplona, Spain

Key Words. Adult bone marrow stem cells • Label • Bromodeoxyuridine • Thymidine analog • Control • Transplantation • Neural differentiation • In vivo tracking

Correspondence: Catherine M. Verfaillie, M.D., Stem Cell Institute, Department of Medicine, University of Minnesota, 420 Delaware Street, Minneapolis, Minnesota 55455, USA. Telephone: 612-625-0602; Fax: 612-624-2436; e-mail: verfa001{at}umn.edu

Received September 22, 2005; accepted for publication December 5, 2005.
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.

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