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Mesenchymal stem cells show radioresistance in vivo.

Singh S, Kloss FR, Brunauer R, Schimke M, Jamnig A, Greiderer-Kleinlercher B, Klima G, Rentenberger J, Auberger T, Hächl O, Rasse M, Gassner R, Lepperdinger G - J. Cell. Mol. Med. (2012)

Bottom Line: When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.

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Properties of primary porcine mesenchymal stromal cells isolated from the mandible directly after irradiation with the indicated effective biological dosage. (A) The proliferation potential was monitored in long-term culture. (B) Colony formation was accounted in low-density secondary culture. (C) After irradiation and subsequent cultivation in the presence of osteogenic induction medium, the differentiation potential was assessed in triplicates (for grading, see left panel). For specification of arbitrary units, see Materials and methods. Experimental results in bar graphs are shown as mean ± standard deviation.
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fig05: Properties of primary porcine mesenchymal stromal cells isolated from the mandible directly after irradiation with the indicated effective biological dosage. (A) The proliferation potential was monitored in long-term culture. (B) Colony formation was accounted in low-density secondary culture. (C) After irradiation and subsequent cultivation in the presence of osteogenic induction medium, the differentiation potential was assessed in triplicates (for grading, see left panel). For specification of arbitrary units, see Materials and methods. Experimental results in bar graphs are shown as mean ± standard deviation.

Mentions: This observation prompted us to consider in vivo irradiated MSC as an indicator for vitality after treatment. Similar to the observations in vitro, MSC suffer damage, resulting in attenuation of cell intrinsic osteogenic differentiation capacity in vivo. To determine the impact of ionizing radiation on MSC that are borne within bone and bone marrow, mandible biopsies were taken from living animals directly after irradiation with a single dose of 9 or 18 Gy, the latter accounting for a BED of 60 Gy. Notably, long-term proliferation capacity of isolated MSC, which survived the radiation treatment, was comparable to those of non-irradiated counterparts (Fig. 5A). MSC, which had been isolated directly after the animals received a 9 Gy dose, exhibited no difference in colony forming capability, and also osteogenic potential was comparable to non-irradiated controls (Fig. 5B and C). These results suggested that a 9 Gy treatment is tolerated in as much pig mandible and surrounding tissue still contained viable cells, although at decreased numbers, which still exhibited long-term proliferation potential and osteogenic differentiation capacity. Moreover, the tissue showed no obvious signs of exuberant necrosis and only mild enduring inflammation became apparent. Yet, after irradiation with a single dose of 18 Gy MSC numbers were greatly reduced (Fig. 5B) and although isolated MSC still exhibited uninterrupted long-term proliferation potential (Fig. 5A), cellular properties were greatly affected as their osteogenic differentiation potential was attenuated (Fig. 5C). Conspicuously, MSC tolerate irradiation up to 9 Gy.


Mesenchymal stem cells show radioresistance in vivo.

Singh S, Kloss FR, Brunauer R, Schimke M, Jamnig A, Greiderer-Kleinlercher B, Klima G, Rentenberger J, Auberger T, Hächl O, Rasse M, Gassner R, Lepperdinger G - J. Cell. Mol. Med. (2012)

Properties of primary porcine mesenchymal stromal cells isolated from the mandible directly after irradiation with the indicated effective biological dosage. (A) The proliferation potential was monitored in long-term culture. (B) Colony formation was accounted in low-density secondary culture. (C) After irradiation and subsequent cultivation in the presence of osteogenic induction medium, the differentiation potential was assessed in triplicates (for grading, see left panel). For specification of arbitrary units, see Materials and methods. Experimental results in bar graphs are shown as mean ± standard deviation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822856&req=5

fig05: Properties of primary porcine mesenchymal stromal cells isolated from the mandible directly after irradiation with the indicated effective biological dosage. (A) The proliferation potential was monitored in long-term culture. (B) Colony formation was accounted in low-density secondary culture. (C) After irradiation and subsequent cultivation in the presence of osteogenic induction medium, the differentiation potential was assessed in triplicates (for grading, see left panel). For specification of arbitrary units, see Materials and methods. Experimental results in bar graphs are shown as mean ± standard deviation.
Mentions: This observation prompted us to consider in vivo irradiated MSC as an indicator for vitality after treatment. Similar to the observations in vitro, MSC suffer damage, resulting in attenuation of cell intrinsic osteogenic differentiation capacity in vivo. To determine the impact of ionizing radiation on MSC that are borne within bone and bone marrow, mandible biopsies were taken from living animals directly after irradiation with a single dose of 9 or 18 Gy, the latter accounting for a BED of 60 Gy. Notably, long-term proliferation capacity of isolated MSC, which survived the radiation treatment, was comparable to those of non-irradiated counterparts (Fig. 5A). MSC, which had been isolated directly after the animals received a 9 Gy dose, exhibited no difference in colony forming capability, and also osteogenic potential was comparable to non-irradiated controls (Fig. 5B and C). These results suggested that a 9 Gy treatment is tolerated in as much pig mandible and surrounding tissue still contained viable cells, although at decreased numbers, which still exhibited long-term proliferation potential and osteogenic differentiation capacity. Moreover, the tissue showed no obvious signs of exuberant necrosis and only mild enduring inflammation became apparent. Yet, after irradiation with a single dose of 18 Gy MSC numbers were greatly reduced (Fig. 5B) and although isolated MSC still exhibited uninterrupted long-term proliferation potential (Fig. 5A), cellular properties were greatly affected as their osteogenic differentiation potential was attenuated (Fig. 5C). Conspicuously, MSC tolerate irradiation up to 9 Gy.

Bottom Line: When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.

Show MeSH
Related in: MedlinePlus