In vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models

Todd E. Meyerrose, Daniel A. De Ugarte, A. Alex Hofling, Phillip E. Herrbrich, Taylor D. Cordonnier, Leonard D. Shultz, J. Chris Eagon, Louisa Wirthlin, Mark S. Sands, Marc A. Hedrick, Jan Nolta

Research output: Contribution to journalArticle

139 Scopus citations

Abstract

The potential for human adipose-derived mesenchymal stem cells (AMSC) to traffic into various tissue compartments was examined using three murine xenotransplantation models: nonobese diabetic/severe combined immunodeficient (NOD/SCID), nude/NOD/SCID, and NOD/SCID/MPSVII mice. Enhanced green fluorescent protein was introduced into purified AMSC via retroviral vectors to assist in identification of cells after transplantation. Transduced cells were administered to sublethally irradiated immune-deficient mice through i.v., intraperitoneal, or subcutaneous injection. Up to 75 days after transplantation, tissues were harvested and DNA polymerase chain reaction (PCR) was performed for specific vector sequences as well as for human Alu repeat sequences. Duplex quantitative PCR using human β-globin and murine rapsyn primers assessed the contribution of human cells to each tissue. The use of the novel NOD/SCID/MPSVII mouse as a recipient allowed rapid identification of human cells in the murine tissues, using an enzyme reaction that was independent of surface protein expression or transduction with an exogenous transgene. For up to 75 days after transplantation, donor-derived cells were observed in multiple tissues, consistently across the various administration routes and independent of transduction parameters. Tissue localization studies showed that the primary MSC did not proliferate extensively at the sites of lodgement. We conclude that human AMSC represent a population of stem cells with a ubiquitous pattern of tissue distribution after administration. AMSC are easily obtained and highly amenable to current transduction protocols for retroviral transduction, making them an excellent avenue for cell-based therapies that involve a wide range of end tissue targets.

Original languageEnglish (US)
Pages (from-to)220-227
Number of pages8
JournalStem Cells
Volume25
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Keywords

  • Adult stem cells
  • Ex vivo gene transfer
  • Human
  • Immunodeficient mouse
  • Mesenchymal stem cells in vivo tracking
  • Stem cell transplantation
  • Xenogeneic stem cell transplantation

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Meyerrose, T. E., De Ugarte, D. A., Hofling, A. A., Herrbrich, P. E., Cordonnier, T. D., Shultz, L. D., Eagon, J. C., Wirthlin, L., Sands, M. S., Hedrick, M. A., & Nolta, J. (2007). In vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models. Stem Cells, 25(1), 220-227. https://doi.org/10.1634/stemcells.2006-0243