Quantitative tools for assessing the fate of xenotransplanted human stem/progenitor cells in chimeric mice

Kang Cheng, Sanjeev Gupta

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: Identification of transplanted human cells in mouse models is important for studying the biology and therapeutic potential of stem/progenitor cells. As stem/progenitor cells are often transplanted in low numbers, detection of cell engraftment requires sensitive tools. Probes for single copy genes, as well as repetitive genetic elements are available for detecting transplanted cells, although their value relative to one another had not been defined. Methods: We examined whether human sequences in chimeric mice could be measured with quantitative real-time polymerase chain reactions for Charcot-Marie-Tooth disease, type 1 repeat element, sex-determining region Y, or short tandem repeats (STR) across human leukocyte antigen (HLA) regions, which are distinct from rodent genomes. Results: We found that specific probes for all three candidate approaches successfully identified human cells in mixtures containing human and mouse genomes. However, probes for Charcot-Marie-Tooth disease element or STRs for HLA regions were less effective for low numbers of transplanted human stem/progenitor cells in mice than human sex-determining region on Y-chromosome. None of the approaches could identify transplanted human cells constituting less than one percent of the total cell mass. This required localization of transplanted cells in tissue sections with human-specific in situ hybridization probes. Conclusions: Quantitative assays with probes for single copy gene sequences, STRs or sex-determining region will be helpful for demonstrating organ repopulation, although initial lower frequency engraftment of human cells in chimeric mice will be most effectively identified by complementary tools, such as in situ localization of human cells in tissues.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalXenotransplantation
Volume16
Issue number3
DOIs
StatePublished - May 1 2009

Keywords

  • Cell transplantation
  • Detection
  • Human
  • Mouse
  • Stem cells

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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