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Xanthosine administration does not affect the proportion of epithelial stem cells in bovine mammary tissue, but has a latent negative effect on cell proliferation.

Abstract
The challenge in manipulating the proportion of somatic stem cells lies in having to override tissue homeostasis. Xanthosine infusion via the teat canal has been reported to augment the number of label-retaining cells in the mammary gland of 3-month-old bovine calves. To further delineate xanthosine׳s effect on defined stem cells in the mammary gland of heifers-which are candidates for increased prospective milk production following such manipulation-bovine mammary parenchymal tissue was transplanted and integrated into the cleared mammary fat pad of immunodeficient mice. Xanthosine administration for 14 days did not affect the number of label-retaining cells after 10- and 11-week chases. No change in stem cell proportion, analyzed according to CD49f and CD24 expression, was noted. Clone formation and propagation rate of cultured cells, as well as expression of stem cell markers, were also unaffected. In contrast, a latent 50% decrease in bovine mammary cell proliferation rate was observed 11 weeks after xanthosine administration. Tumor development in mice was also limited by xanthosine administration. These effects may have resulted from an initial decrease in expression of the rate-limiting enzyme in guanine synthesis, IMPDH. The data indicate that caution should be exerted when considering xanthosine for stem cell manipulation.
AuthorsGat Rauner, Itamar Barash
JournalExperimental cell research (Exp Cell Res) Vol. 328 Issue 1 Pg. 186-196 (Oct 15 2014) ISSN: 1090-2422 [Electronic] United States
PMID24992045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • RNA, Messenger
  • Ribonucleosides
  • Xanthines
  • xanthosine
Topics
  • Animals
  • Apoptosis (drug effects)
  • Blotting, Western
  • Cattle
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Epithelial Cells (cytology, drug effects)
  • Female
  • Flow Cytometry
  • Immunoenzyme Techniques
  • Mammary Glands, Animal (cytology, drug effects)
  • Mammary Neoplasms, Experimental (drug therapy, pathology)
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleosides (administration & dosage, pharmacology)
  • Stem Cells (cytology, drug effects)
  • Xanthines

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