Alexander Rühle1, Oliver Xia1, Ramon Lopez Perez2, Thuy Trinh3, Wiltrud Richter4, Anna Sarnowska5, Patrick Wuchter6, Jürgen Debus1, Rainer Saffrich7, Peter E Huber1, Nils H Nicolay8. 1. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 2. Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 3. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. 4. Research Center for Experimental Orthopedics, Heidelberg University Hospital, Heidelberg, Germany. 5. Translative Platform for Regenerative Medicine, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. 6. Institute of Transfusion Medicine and Immunology, German Red Cross Donor Blood Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. 7. Institute of Transfusion Medicine and Immunology, German Red Cross Donor Blood Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany. 8. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: n.nicolay@dkfz.de.
Abstract
PURPOSE: Human mesenchymal stromal cells (MSCs) may aid the regeneration of ionizing radiation (IR)-induced tissue damage. They can be harvested from different tissues for clinical purposes; however, the role of the tissue source on the radiation response of human MSCs remains unknown. METHODS AND MATERIALS: Human MSCs were isolated from adipose tissue, bone marrow, and umbilical cord, and cellular survival, proliferation, and apoptosis were measured after irradiation. The influence of IR on the defining functions of MSCs was assessed, and cell morphology, surface marker expression, and the differentiation potential were examined. Western blot analyses were performed to assess the activation of DNA damage signaling and repair pathways. RESULTS: MSCs from adipose tissue, bone marrow, and umbilical cord exhibited a relative radioresistance independent of their tissue of origin. Defining properties including cellular adhesion and surface marker expression were preserved, and irradiated MSCs maintained their potential for multilineage differentiation irrespective of their tissue source. Analysis of activated DNA damage recognition and repair pathways demonstrated an efficient repair of IR-induced DNA double-strand breaks in MSCs from different tissues, thereby influencing the induction of apoptosis. CONCLUSIONS: These data show for the first time that MSCs are resistant to IR and largely preserve their defining functions after irradiation irrespective of their tissue of origin. Efficient repair of IR-induced DNA double-strand breaks and consecutive reduction of apoptosis induction may contribute to the tissue-independent radiation resistance of MSCs.
PURPOSE:Human mesenchymal stromal cells (MSCs) may aid the regeneration of ionizing radiation (IR)-induced tissue damage. They can be harvested from different tissues for clinical purposes; however, the role of the tissue source on the radiation response of human MSCs remains unknown. METHODS AND MATERIALS: Human MSCs were isolated from adipose tissue, bone marrow, and umbilical cord, and cellular survival, proliferation, and apoptosis were measured after irradiation. The influence of IR on the defining functions of MSCs was assessed, and cell morphology, surface marker expression, and the differentiation potential were examined. Western blot analyses were performed to assess the activation of DNA damage signaling and repair pathways. RESULTS: MSCs from adipose tissue, bone marrow, and umbilical cord exhibited a relative radioresistance independent of their tissue of origin. Defining properties including cellular adhesion and surface marker expression were preserved, and irradiated MSCs maintained their potential for multilineage differentiation irrespective of their tissue source. Analysis of activated DNA damage recognition and repair pathways demonstrated an efficient repair of IR-induced DNA double-strand breaks in MSCs from different tissues, thereby influencing the induction of apoptosis. CONCLUSIONS: These data show for the first time that MSCs are resistant to IR and largely preserve their defining functions after irradiation irrespective of their tissue of origin. Efficient repair of IR-induced DNA double-strand breaks and consecutive reduction of apoptosis induction may contribute to the tissue-independent radiation resistance of MSCs.
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: Aranee Sivananthan; Donna Shields; Renee Fisher; Wen Hou; Xichen Zhang; Darcy Franicola; Michael W Epperly; Peter Wipf; Joel S Greenberger Journal: Radiat Res Date: 2018-11-30 Impact factor: 2.841
Authors: Nils H Nicolay; Nicole Wiedenmann; Michael Mix; Wolfgang A Weber; Martin Werner; Anca L Grosu; Gian Kayser Journal: Eur J Nucl Med Mol Imaging Date: 2019-12-07 Impact factor: 9.236
Authors: Ramon Lopez Perez; Jannek Brauer; Alexander Rühle; Thuy Trinh; Sonevisay Sisombath; Patrick Wuchter; Anca-Ligia Grosu; Jürgen Debus; Rainer Saffrich; Peter E Huber; Nils H Nicolay Journal: Sci Rep Date: 2019-12-27 Impact factor: 4.379
Authors: Niels Belmans; Liese Gilles; Jonas Welkenhuysen; Randy Vermeesen; Bjorn Baselet; Benjamin Salmon; Sarah Baatout; Reinhilde Jacobs; Stéphane Lucas; Ivo Lambrichts; Marjan Moreels Journal: Front Public Health Date: 2021-02-15