title: Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome.
abstract: 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.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, IRSN/DPHD/ SARAM, Fontenay aux roses, France. alain.chapel@irsn.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Chapel
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Bertho
authors.forename: Morad
authors.initials: M
authors.lastname: Bensidhoum
authors.forename: Loic
authors.initials: L
authors.lastname: Fouillard
authors.forename: Randell G
authors.initials: RG
authors.lastname: Young
authors.forename: Johanna
authors.initials: J
authors.lastname: Frick
authors.forename: Christelle
authors.initials: C
authors.lastname: Demarquay
authors.forename: Frédérique
authors.initials: F
authors.lastname: Cuvelier
authors.forename: Emilie
authors.initials: E
authors.lastname: Mathieu
authors.forename: François
authors.initials: F
authors.lastname: Trompier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dudoignon
authors.forename: Claire
authors.initials: C
authors.lastname: Germain
authors.forename: Christelle
authors.initials: C
authors.lastname: Mazurier
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Aigueperse
authors.forename: Jade
authors.initials: J
authors.lastname: Borneman
authors.forename: Norbert Claude
authors.initials: NC
authors.lastname: Gorin
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.forename: Dominique
authors.initials: D
authors.lastname: Thierry
mesh_terms: 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
chemical_list: D005819:Genetic Markers; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins