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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-06-1830.

Submitted June 20, 2002
Accepted November 22, 2002
Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into non-human primates
Steven M Devine*, Carrington Cobbs, Matt Jennings, Amelia Bartholomew, and Ronald Hoffman
Hematology/Oncology, University of Illinois at Chicago, Chicago, IL, USA
Osiris Therapeutics, Inc., Baltimore, MD, USA
Surgery, University of Illinois at Chicago, Chicago, IL, USA
* Corresponding author; email: sdevine{at}im.wustl.edu.
Ex vivo expanded mesenchymal stem cells (MSC) were transduced with a green fluorescent protein (GFP) retroviral construct and subsequently infused into three adult baboons following lethal total body irradiation and hematopoietic support (2) or without any prior conditioning (1). In order to study the long term fate of these MSC, necropsies were performed between 9 and 21 months following MSC infusion and an average of 16 distinct tissues were recovered from each recipient and evaluated for the presence of the GFP transgene in purified genomic DNA by sensitive real time PCR. Two baboons received autologous and one allogeneic GFP-transduced MSC. Both allogeneic and autologous MSC appeared to distribute in a similar manner. Gastrointestinal tissues harbored high concentrations of transgene per microgram of DNA. Additional tissues including kidney, lung, liver, thymus, and skin were also found to contain relatively high amounts of DNA equivalents. Estimated levels of engraftment in these tissues ranged from 0.1 to 2.7%. The non-conditioned recipient appeared to have less abundant engraftment. These data suggest that MSC initially distribute broadly following systemic infusion and later may participate in ongoing cellular turnover and replacement in a wide variety of tissues.

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