title: Mesenchymal stem cells show radioresistance in vivo.
abstract: Irradiation impacts on the viability and differentiation capacity of tissue-borne mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. As a consequence of radiotherapy, bones may develop osteoradionecrosis. When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced. Mitotically stalled cells were still capable of differentiating into osteoblasts and pre-adipocytes. As a large animal model comparable to the clinical situation, pig mandibles were subjected to fractionized radiation of 2 χ 9 Gy within 1 week. This treatment mimics that of a standardized clinical treatment regimen of head and neck cancer patients irradiated 30 χ 2 Gy. In the pig model, fractures which had been irradiated, showed delayed osseous healing. When isolating MSC at different time points post-irradiation, no significant changes regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with a single dose of either 9 or 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first 2 weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can effectively cope with irradiation up to high doses in vivo. This finding should thus be implemented in future therapeutic concepts to protect regenerating tissue from radiation consequences.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
authors.forename: Sarvpreet
authors.initials: S
authors.lastname: Singh
authors.forename: Frank R
authors.initials: FR
authors.lastname: Kloss
authors.forename: Regina
authors.initials: R
authors.lastname: Brunauer
authors.forename: Magdalena
authors.initials: M
authors.lastname: Schimke
authors.forename: Angelika
authors.initials: A
authors.lastname: Jamnig
authors.forename: Brigitte
authors.initials: B
authors.lastname: Greiderer-Kleinlercher
authors.forename: Günter
authors.initials: G
authors.lastname: Klima
authors.forename: Julia
authors.initials: J
authors.lastname: Rentenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Auberger
authors.forename: Oliver
authors.initials: O
authors.lastname: Hächl
authors.forename: Michael
authors.initials: M
authors.lastname: Rasse
authors.forename: Robert
authors.initials: R
authors.lastname: Gassner
authors.forename: Günter
authors.initials: G
authors.lastname: Lepperdinger
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000528:radiation effects*; D016133:Polymerase Chain Reaction; D011836:Radiation Tolerance; D013552:Swine