Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome
Résumé
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.
| Origine | Fichiers produits par l'(les) auteur(s) |
|---|
