Adipose mesenchymal stromal cells response to ionizing radiation

Maria, Osama Muhammad; Kumala, Sławomir; Heravi, Mitra; Syme, Alasdair; Eliopoulos, Nicoletta; Muanza, Thierry

doi:10.1016/j.jcyt.2015.12.001

Cited by 18 publications

(24 citation statements)

References 56 publications

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“…It has been suggested that DSB in MSCs are repaired by activation of both the homologous recombination (HR, during S and G2 phases) and the non-homologous end-joining (NHEJ, during all cell cycle phases) DNA repair pathways [95,104,106]. Our recent study showed the activation of HR and NHEJ repair pathways in irradiated aMSCs [159]. In addition, P-ATM enhances the stabilization of the tumor suppressor regulatory protein and transcription factor P53 which up-regulates the expression and enhances the stabilization of the transcription factor and inhibitory regulatory protein p21, which potently inhibits Cdks which are needed for the G1/S transition leading to inhibition of the entry into S phase [106].…”

Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 77%

“…In radiation-induced normal tissue injury, aMSCs have shown significant repair of cutaneous radiation syndrome [79][80][81][82][83] and photo-aging [84], RT-induced acute salivary gland [85] and intestine injuries [70,[86][87][88], and chronic injuries induced by radiotherapy [80,89]. In addition, we have shown in a previous study that aMSCs are relatively resistant to ionizing radiation, a property that qualifies them to be a reliable cellular therapy candidate before and during RT [159].…”

Section: Methodsmentioning

confidence: 98%

“…The application of MSCs in radiation oncology regenerative medicine (RORM) was enhanced by their efficient radiation-induced DNA repair machinery and their relative radiation resistance [91,95,96,99,159]. Such radiation resistance was mediated by many mechanisms, e.g.…”

Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 99%

“…Such radiation resistance was mediated by many mechanisms, e.g. the ATM phosphorylation, activation of cell cycle check points (G2/M arrest), and activation of single and double stranded DNA repair by both homologous and non-homologous recombination mechanisms and other pathways [95,159] (Figure.3.4.1). DSB resulting from the direct and indirect radiation injury stimulate the phosphorylation of ATM which is the proximal step for cell cycle check point's activation (G2/M arrest).…”

Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 99%

“…In addition to that, the nuclear apoptotic factor P84 (P84/53E10 = the nuclear protein encoded by the N5 gene) is up regulated, which participates in the apoptotic response of the aMSCs. It has been documented that irradiated aMSCs showed p-ATM dependent and p-ATM independent (P84-mediated) G2/M arrest [159]. Phosphorylated histone-2AX (γ-H2AX) stimulated both the HR and the NHEJ of the dsDNA breaks and other repair mechanisms [160].…”

Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 99%

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Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

et al. 2016

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Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 77%

Section: Methodsmentioning

confidence: 98%

Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 99%

Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 99%

Section: Mesenchymal Stromal Cells (Mscs) Radio-biological Responsementioning

confidence: 99%

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Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

et al. 2016

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Radiation‐induced sensitivity of tissue‐resident mesenchymal stem cells in the head and neck region

Spiegel¹,

Hambrecht²,

Kohlbauer³

et al. 2019

Head & Neck

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Background Tissue‐resident mesenchymal stem cells (MSCs) possess the ability to migrate to areas of inflammation and promote the regeneration of damaged tissue. However, it remains unclear how radiation influences this capacity of MSC in the head and neck region. Methods Two types of MSCs of the head and neck region (mucosa [mMSC] and parotid gland [pMSC]) were isolated, cultured and exposed to single radiation dosages of 2 Gy/day up to 10 days. Effects on morphology, colony forming ability, apoptosis, chemokine receptor expression, cytokine secretion, and cell migration were analyzed. Results Although MSC preserved MSC‐specific regenerative abilities and immunomodulatory properties following irradiation in our in vitro model, we found a deleterious impact on colony forming ability, especially in pMSC. Conclusions MSC exhibited robustness and activation upon radiation for the support of tissue regeneration, but lost their potential to replicate, thus possibly leading to depletion of the local MSC‐pool after irradiation

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Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells

et al. 2017

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Background Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high‐risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next‐generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy. Methods Using a number of androgen‐dependent (LNCaP, PC3‐T877A) and androgen‐independent (C4‐2, 22RV1, PC3, PC3‐AR V7) cell lines, the effect of ENZA as a radiosensitizer was studied alone or in combination with ADT and/or XRT. Cell viability and cell survival were assessed, along with determination of cell cycle arrest, DNA damage response and repair, apoptosis and senescence. Results Our results indicated that either ENZA alone (in AR positive, androgen‐dependent PCa cells) or in combination with ADT (in AR positive, hormone‐insensitive PCa cells) potentiates radiation response [Dose enhancement factor (DEF) of 1.75 in LNCAP and 1.35 in C4‐2] stronger than ADT + XRT conditions. Additionally, ENZA sensitized androgen dependent PCa cells to XRT in a schedule‐dependent manner, where concurrent administration of ENZA and radiation lead to a maximal radiosensitization when compared to either drug administration prior or after XRT. In LNCaP cells, ENZA treatment significantly prolonged the presence of XRT‐induced phospho‐γH2AX up to 24 h after treatment; suggesting enhanced DNA damage. It also significantly increased XRT‐induced apoptosis and senescence. Conclusions Our data indicates that ENZA acts as a much stronger radiosensitizer compared to ADT. We have also observed that its efficacy is schedule dependent and related to increased levels of DNA damage and a delay of DNA repair processes. Finally, the initial abrogation of DNA‐PKcs activity by AR inhibition and its subsequent recovery might represent an important mechanism by which PCa cells acquire resistance to combined anti‐androgen and XRT treatment. This work suggests a new use of ENZA in combination with XRT that could be applicable in clinical trial settings for patients with early and intermediate hormone responsive disease.

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Adipose mesenchymal stromal cells response to ionizing radiation

Cited by 18 publications

References 56 publications

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

Radiation‐induced sensitivity of tissue‐resident mesenchymal stem cells in the head and neck region

Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells

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