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TRANSLATIONAL AND CLINICAL RESEARCH

In Vivo Distribution of Human Adipose-Derived Mesenchymal Stem Cells in Novel Xenotransplantation Models

^aWashington University School of Medicine, Division of Oncology, Hematopoietic Development and Malignancy Section, St. Louis, Missouri, USA;
^bUCLA School of Medicine, Department of Surgery, Regenerative Bioengineering and Repair Laboratory, Los Angeles, California, USA;
^cThe Jackson Laboratory, Bar Harbor, Maine, USA;
^dWashington University School of Medicine, Division of General Surgery, Department of Surgery, St. Louis, Missouri, USA;
^eCytori Therapeutics, Inc., San Diego, California, USA

Key Words. Adult stem cells • Xenogeneic stem cell transplantation • Stem cell transplantation • Mesenchymal stem cells In vivo tracking • Immunodeficient mouse • Human • Ex vivo gene transfer

Correspondence: Jan A. Nolta, Ph.D., Washington University School of Medicine, Department of Internal Medicine, Division of Oncology, Hematopoietic Development and Malignancy Section, Southwest Tower, 6th floor, Room 643, 4940 Parkview Place, St. Louis, Missouri 63110, USA. Telephone: 314-362-3123; Fax: 314-362-9333; e-mail: jnolta{at}im.wustl.edu

Received April 20, 2006; accepted for publication August 23, 2006.
First published online in STEM CELLS EXPRESS   September 7, 2006.



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 ß-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.

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