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000180796 1001_ $$0P:(DE-He78)80e100a16534f5fc67f7436ee67a47f9$$aRühle, Alexander$$b0$$eFirst author$$udkfz
000180796 245__ $$aHuman Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma.
000180796 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2022
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000180796 520__ $$aRadiotherapy of head-and-neck squamous cell carcinoma (HNSCC) can cause considerable normal tissue injuries, and mesenchymal stromal cells (MSCs) have been shown to aid regeneration of irradiation-damaged normal tissues. However, utilization of MSC-based treatments for HNSCC patients undergoing radiotherapy is hampered by concerns regarding potential radioprotective effects. We therefore investigated the influence of MSCs on the radiosensitivity of HNSCCs. Several human papillomavirus (HPV)-negative and HPV-positive HNSCCs were co-cultured with human bone marrow-derived MSCs using two-dimensional and three-dimensional assays. Clonogenic survival, proliferation, and viability of HNSCCs after radiotherapy were assessed depending on MSC co-culture. Flow cytometry analyses were conducted to examine the influence of MSCs on irradiation-induced cell cycle distribution and apoptosis induction in HNSCCs. Immunofluorescence stainings of γH2AX were conducted to determine the levels of residual irradiation-induced DNA double-strand breaks. Levels of connective tissue growth factor (CTGF), a multifunctional pro-tumorigenic cytokine, were analyzed using enzyme-linked immunosorbent assays. Neither direct MSC co-culture nor MSC-conditioned medium exerted radioprotective effects on HNSCCs as determined by clonogenic survival, proliferation, and viability assays. Consistently, three-dimensional microwell arrays revealed no radioprotective effects of MSCs. Irradiation resulted in a G2/M arrest of HNSCCs at 96 h independently of MSC co-culture. HNSCCs' apoptosis rates were increased by irradiation irrespective of MSCs. Numbers of residual γH2AX foci after irradiation with 2 or 8 Gy were comparable between mono- and co-cultures. MSC mono-cultures and HNSCC-MSC co-cultures exhibited comparable CTGF levels. We did not detect radioprotective effects of human MSCs on HNSCCs. Our results suggest that the usage of MSC-based therapies for radiotherapy-related toxicities in HNSCC patients may be safe in the context of absent radioprotection.
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000180796 650_7 $$2Other$$aco-culture
000180796 650_7 $$2Other$$ahead-and-neck cancer
000180796 650_7 $$2Other$$ahead-and-neck squamous cell carcinoma
000180796 650_7 $$2Other$$amesenchymal stromal cells
000180796 650_7 $$2Other$$aradioresistance
000180796 650_7 $$2Other$$aradiosensitivity
000180796 650_7 $$2Other$$aradiotherapy
000180796 7001_ $$0P:(DE-HGF)0$$aLies, Marie$$b1
000180796 7001_ $$0P:(DE-HGF)0$$aStrack, Maren$$b2
000180796 7001_ $$0P:(DE-HGF)0$$aPerez, Ramon Lopez$$b3
000180796 7001_ $$0P:(DE-HGF)0$$aBieber, Birgit$$b4
000180796 7001_ $$00000-0002-0163-8677$$aThomsen, Andreas R$$b5
000180796 7001_ $$00000-0001-8558-0347$$aBronsert, Peter$$b6
000180796 7001_ $$0P:(DE-He78)3291aaac20f3d603d96744c1f0890028$$aHuber, Peter$$b7$$udkfz
000180796 7001_ $$0P:(DE-He78)2e5f34f1c58eda4787a14c9dc139ca5f$$aHess, Jochen$$b8$$udkfz
000180796 7001_ $$aKnopf, Andreas$$b9
000180796 7001_ $$aWuchter, Patrick$$b10
000180796 7001_ $$0P:(DE-HGF)0$$aGrosu, Anca-Ligia$$b11
000180796 7001_ $$0P:(DE-He78)8d52e7ff1ccaac7dbf0232fdcb0168bd$$aNicolay, Nils$$b12$$eLast author$$udkfz
000180796 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms23147689$$gVol. 23, no. 14, p. 7689 -$$n14$$p7689$$tInternational journal of molecular sciences$$v23$$x1422-0067$$y2022
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