In vivo Distribution of Human Adipose-Derived MSC

¹ Washington University School of Medicine, Division of Oncology, Hematopoietic Development and Malignancy Section, Saint Louis, Missouri
² University of California at Los Angeles, School of Medicine, Department of Surgery, Regenerative Bioengineering and Repair Laboratory, Los Angeles, California
³ The Jackson Laboratory, Bar Harbor, Maine
⁴ University of California at Los Angeles, School of Medicine, Department of Surgery, Regenerative Bioengineering and Repair Laboratory, Los Angeles, California; Cytori Therapeutics, Inc., San Diego, California

^* To whom correspondence should be addressed. E-mail: jnolta{at}im.wustl.edu.

	Abstract

The potential for human adipose-derived mesenchymal stem cells (AMSC) to traffic into various tissue compartments was examined using three murine xenotransplantation models: NOD/SCID, nude/NOD/SCID and NOD/SCID/MPSVII mice. Enhanced green fluorescent protein (eGFP) was introduced into purified AMSC via retroviral vectors to assist in identification of cells post-transplantation. Transduced cells were administered to sub-lethally irradiated immune deficient mice through intravenous, intraperitoneal, or subcutaneous injection. Up to 75 days post-transplantation, tissues were harvested and DNA PCR was performed for specific vector sequences as well as for human Alu repeat sequences. Duplex quantitative PCR using human B-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 post-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.