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Mesenchymal stem cells home to injured tissues when co‐infused with hematopoietic cells to treat a radiation‐induced multi‐organ failure syndrome
Author(s) -
Chapel Alain,
Bertho Jean Marc,
Bensidhoum Morad,
Fouillard Loic,
Young Randell G.,
Frick Johanna,
Demarquay Christelle,
Cuvelier Frédérique,
Mathieu Emilie,
Trompier François,
Dudoig Nicolas,
Germain Claire,
Mazurier Christelle,
Aigueperse Jocelyne,
Borneman Jade,
Gorin Norbert Claude,
Gourmelon Patrick,
Thierry Dominique
Publication year - 2003
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.452
Subject(s) - mesenchymal stem cell , homing (biology) , bone marrow , haematopoiesis , ex vivo , stem cell , acute radiation syndrome , medicine , pathology , in vivo , cancer research , biology , microbiology and biotechnology , ecology
Background Recent studies have suggested that ex vivo expansion of autologous hematopoietic cells could be a therapy of choice for the treatment of bone marrow failure. We investigated the potential of a combined infusion of autologous ex vivo expanded hematopoietic cells with mesenchymal (MSCs) for the treatment of multi‐organ failure syndrome following irradiation in a non‐human primate model. Methods Hematopoietic cells and MSCs were expanded from bone marrow aspirates. MSCs were transduced with the gene encoding for the green fluorescent protein (e‐GFP), in order to track them following infusion. Twelve animals were studied. Nine animals received total‐body irradiation at 8 Gy from a neutron/gamma source thus resulting in heterogeneous exposure; three animals were sham‐irradiated. The animals were treated with expanded hematopoietic stem cells and MSCs, expanded hematopoietic stem cells alone, or MSCs alone. Unmanipulated bone marrow cell transplants were used as controls. Results Depending on the neutron/gamma ratio, an acute radiation sickness of varying severity but of similar nature resulted. GFP‐labeled cells were found in the injured muscle, skin, bone marrow and gut of the treated animals via PCR up to 82 days post‐infusion. Conclusions This is the first evidence of expanded MSCs homing in numerous tissues following a severe multi‐organ injury in primates. Localization of the transduced MSCs correlated to the severity and geometry of irradiation. A repair process was observed in various tissues. The plasticity potential of the MSCs and their contribution to the repair process in vivo remains to be studied. Copyright © 2003 John Wiley & Sons, Ltd.