title: Mesenchymal stem cells retain their defining stem cell characteristics after exposure to ionizing radiation.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown.
  
  
  METHODS
  Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays.
  
  
  RESULTS
  MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR.
  
  
  CONCLUSIONS
  These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression.
authors.affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany. Electronic address: n.nicolay@dkfz.de.
authors.forename: Nils H
authors.initials: NH
authors.lastname: Nicolay
authors.affiliation: Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Sommer
authors.affiliation: Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ramon
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Wirkner
authors.affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Thuy
authors.initials: T
authors.lastname: Trinh
authors.affiliation: Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Sonevisay
authors.initials: S
authors.lastname: Sisombath
authors.affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.affiliation: Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D015415:Biomarkers / Q000032:analysis; D002448:Cell Adhesion / Q000502:physiology / Q000528:radiation effects; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects; D002465:Cell Movement / Q000502:physiology / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D015870:Gene Expression; D064368:Healthy Volunteers; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology / Q000528:radiation effects*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing
chemical_list: D015415:Biomarkers