Nils H Nicolay1, Eva Sommer2, Ramon Lopez2, Ute Wirkner2, Thuy Trinh3, Sonevisay Sisombath2, Jürgen Debus4, Anthony D Ho5, Rainer Saffrich5, Peter E Huber3. 1. 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. 2. Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany. 3. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany. 4. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. 5. Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
Abstract
PURPOSE: 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 AND MATERIALS: 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.
PURPOSE: 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 AND MATERIALS: 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: Alexander Rühle; Ramon Lopez Perez; Bingwen Zou; Anca-Ligia Grosu; Peter E Huber; Nils H Nicolay Journal: Stem Cell Rev Rep Date: 2019-06 Impact factor: 5.739
Authors: Nils H Nicolay; Eva Sommer; Ramon Lopez Perez; Ute Wirkner; Tilman Bostel; Anthony D Ho; Michael Lahn; Jürgen Debus; Rainer Saffrich; Peter E Huber Journal: Strahlenther Onkol Date: 2014-05-27 Impact factor: 3.621
Authors: Thomas Gehrke; Agmal Scherzad; Stephan Hackenberg; Pascal Ickrath; Philipp Schendzielorz; Rudolf Hagen; Norbert Kleinsasser Journal: Oncol Lett Date: 2017-07-18 Impact factor: 2.967
Authors: Nils H Nicolay; Yingying Liang; Ramon Lopez Perez; Tilman Bostel; Thuy Trinh; Sonevisay Sisombath; Klaus-Josef Weber; Anthony D Ho; Jürgen Debus; Rainer Saffrich; Peter E Huber Journal: Oncotarget Date: 2015-02-10
Authors: Lucas K Vitzthum; Helen Park; Kaveh Zakeri; Elena S Heide; Vinit Nalawade; Arno J Mundt; Florin Vaida; James D Murphy; Loren K Mell Journal: Int J Radiat Oncol Biol Phys Date: 2019-10-11 Impact factor: 7.038