Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome.
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.
Chapel
Alain
A
Institut de Radioprotection et de Sûreté Nucléaire, IRSN/DPHD/ SARAM, Fontenay aux roses, France. alain.chapel@irsn.fr
Bertho
Jean Marc
JM
Bensidhoum
Morad
M
Fouillard
Loic
L
Young
Randell G
RG
Frick
Johanna
J
Demarquay
Christelle
C
Cuvelier
Frédérique
F
Mathieu
Emilie
E
Trompier
François
F
Dudoignon
Nicolas
N
Germain
Claire
C
Mazurier
Christelle
C
Aigueperse
Jocelyne
J
Borneman
Jade
J
Gorin
Norbert Claude
NC
Gourmelon
Patrick
P
Thierry
Dominique
D
D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D003131:Combined Modality Therapy; D005819:Genetic Markers; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D008164:Luminescent Proteins / Q000235:genetics; D008252:Macaca fascicularis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009102:Multiple Organ Failure / Q000209:etiology* / Q000628:therapy*; D011832:Radiation Injuries / Q000150:complications* / Q000628:therapy*; D014161:Transduction, Genetic; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D005819:Genetic Markers; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins