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Ionizing Radiation of Mesenchymal Stem Cells Results in Diminution of the Precursor Pool and Limits Potential for Multilineage Differentiation

Schönmeyr, Björn H. M.D.; Wong, Alex K. M.D.; Soares, Marc B.A.; Fernandez, John M.D.; Clavin, Nicholas M.D.; Mehrara, Babak J. M.D.

Plastic and Reconstructive Surgery: July 2008 - Volume 122 - Issue 1 - p 64-76
doi: 10.1097/PRS.0b013e31817743cd
Experimental: Original Articles

Background: Although ionizing radiation is an important treatment modality for a number of malignancies, it can be associated with significant morbidity. The exact mechanisms by which ionizing radiation results in cellular injury remain unknown. Mesenchymal stem cells give rise to a number of tissues including bone, fat, and cartilage and provide an excellent cellular model with which to evaluate the effects of ionizing radiation on cellular survival and function.

Methods: Rat mesenchymal stem cells were irradiated with 0, 7, and 12 Gy of ionizing radiation and assessed for changes in growth, apoptosis, cell-cycle profile, senescence, differentiation, and gene expression.

Results: Ionizing radiation resulted in a significant decrease in cellular proliferation because of increased apoptosis, G2 cell-cycle arrest, and premature senescence. In addition, ionizing radiation caused low-level spontaneous osteoblastic differentiation. Conversely, cellular differentiation in response to lineage-specific culture conditions for bone, fat, and cartilage was markedly decreased in irradiated cells, thereby demonstrating a deficit in the ability of irradiated mesenchymal stem cells to respond to environmental stimuli.

Conclusions: Although the majority of mesenchymal stem cells survive injury from ionizing radiation, this injury results in a significant decrease in cellular proliferation. Furthermore, the differentiation potential of irradiated mesenchymal stem cells in response to environmental stimuli is markedly diminished. Thus, the negative effects of ionizing radiation may result from a decreased pool of progenitor cells with limited differentiation potential. Proposed radioprotection strategies aiming to reduce tissue injury should therefore evaluate not only cellular survival but also cellular function.

New York, N.Y.

From the Division of Plastic and Reconstructive Surgery and the Department of Surgery, Memorial Sloan-Kettering Cancer Center.

Received for publication September 5, 2007; accepted November 8, 2007.

Disclosure: None of the authors has any commercial associations or financial relationships that would create a conflict of interest with the work presented in this article.

Babak J. Mehrara, M.D.; 1275 York Avenue, Room MRI 1005; New York, N.Y. 10021;

©2008American Society of Plastic Surgeons