title: Fractionated doses of ionizing radiation confer protection to mesenchymal stem cell pluripotency.
abstract: BACKGROUND
  Although it is clear that radiation therapy can cause tissue injury, the degree of injury that is observed clinically can be highly variable. It is possible that variability in the methods by which ionizing radiation is delivered can contribute to some of the observed variability. Thus, the purpose of this study was to assess the effects of various fractionation schedules on the growth and differentiation potential of isolated mesenchymal stem cells in vitro.
  
  
  METHODS
  Isolated mesenchymal stem cells (triplicate studies) were exposed to a dose of 12 Gy of ionizing radiation as a single dose, in two doses of 6 Gy, or in six doses of 2 Gy. Cellular proliferation and the potential for differentiation along the bone and fat lineage were assessed. Potential mechanisms for injury and protection were evaluated by analyzing the expression of p21 and manganese superoxide dismutase.
  
  
  RESULTS
  Delivery of radiation in multiple doses confers significant radioprotection to mesenchymal stem cell proliferation and potential for differentiation. In contrast, delivery of 12 Gy of radiation as a single dose or as two equal doses of 6 Gy results in marked deficiencies in cellular proliferation and potential for multilineage cellular differentiation.
  
  
  CONCLUSIONS
  The authors have demonstrated that even minor alterations in fractionation of radiation dose can result in significant effects on the potential of mesenchymal stem cells to differentiate. These findings imply that at least some of the variability in tissue damage after radiation therapy observed clinically may be attributable to differences in the delivery of ionizing radiation.
authors.affiliation: New York, N.Y. From the Plastic and Reconstructive Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Clavin
authors.forename: John
authors.initials: J
authors.lastname: Fernandez
authors.forename: Björn H
authors.initials: BH
authors.lastname: Schönmeyr
authors.forename: Marc A
authors.initials: MA
authors.lastname: Soares
authors.forename: Babak J
authors.initials: BJ
authors.lastname: Mehrara