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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-06-1830.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 2999-3001
HEMATOPOIESIS
Brief report
Mesenchymal stem cells distribute to a wide range of tissues
following systemic infusion into nonhuman primates
Steven M. Devine,
Carrington Cobbs,
Matt Jennings,
Amelia Bartholomew, and
Ron Hoffman
From the Section of Hematology/Oncology, Department of
Surgery, University of Illinois College of Medicine, Chicago; and
Osiris Therapeutics, Baltimore, MD.
Ex vivo-expanded mesenchymal stem cells (MSCs) were transduced
with a green fluorescent protein (GFP) retroviral construct and
subsequently infused into 3 adult baboons following lethal total body
irradiation and hematopoietic support or without any prior
conditioning. To study the long-term fate of these MSCs, 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 polymerase chain reaction (PCR). Two baboons
received autologous and one allogeneic GFP-transduced MSCs. Both
allogeneic and autologous MSCs 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 nonconditioned recipient
appeared to have less abundant engraftment. These data suggest that
MSCs 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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