Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and ionizing radiation

Nicolay, Nils H.; Sommer, Eva; Perez, Ramon Lopez; Wirkner, Ute; Bostel, Tilman; Ho, Anthony D.; Lahn, Michael; Debus, Jürgen; Saffrich, Rainer; Huber, Peter E.

doi:10.1007/s00066-014-0686-1

Cited by 13 publications

(8 citation statements)

References 42 publications

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“…Several analyses have so far provided inconsistent results regarding the sensitivity of MSCs against various chemotherapeutic agents like etoposide, vincristine, cisplatin, kinase inhibitors or ionizing radiation192425262728. A relative in-vitro resistance of MSCs against vincristine, cisplatin or etoposide has been demonstrated in cell culture experiments, and bone marrow samples of patients treated with these drugs have been shown to harbor viable and proliferating MSCs, confirming the observed resistant phenotype in vivo 2930.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells are sensitive to bleomycin treatment

Nicolay

Rühle

Perez

et al. 2016

Sci Rep

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Mesenchymal stem cells (MSCs) have been shown to attenuate pulmonary damage induced by bleomycin-based anticancer treatments, but the influence of bleomycin on the stem cells themselves remains largely unknown. Here, we demonstrate that human bone marrow-derived MSCs are relatively sensitive to bleomycin exposure compared to adult fibroblasts. MSCs revealed increased levels of apoptosis after bleomycin treatment, while cellular morphology, stem cell surface marker expression and the ability for adhesion and migration remained unchanged. Bleomycin treatment also resulted in a reduced adipogenic differentiation potential of these stem cells. MSCs were found to efficiently repair DNA double strand breaks induced by bleomycin, mostly through non-homologous end joining repair. Low mRNA and protein expression levels of the inactivating enzyme bleomycin hydrolase were detected in MSCs that may contribute to the observed bleomycin-sensitive phenotype of these cells. The sensitivity of MSCs against bleomycin needs to be taken into consideration for ongoing and future treatment protocols investigating these stem cells as a potential treatment option for bleomycin-induced pulmonary damage in the clinic.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells are sensitive to bleomycin treatment

Nicolay

Rühle

Perez

et al. 2016

Sci Rep

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“…This analysis compared the effects of photon and carbon ion irradiation on the survival and functional properties of human mesenchymal stem cells. While previous analyses have shown relative radioresistance of MSCs after photon irradiation, no data are available regarding other forms of radiation such as carbon particle radiotherapy despite their clinical use [ 12 , 13 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells are resistant to carbon ion radiotherapy

et al. 2014

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Mesenchymal stem cells (MSCs) participate in regeneration of tissues damaged by ionizing radiation. However, radiation can damage MSCs themselves.Here we show that cellular morphology, adhesion and migration abilities were not measurably altered by photon or carbon ion irradiation. The potential for differentiation was unaffected by either form of radiation, and established MSC surface markers were found to be stably expressed irrespective of radiation treatment. MSCs were able to efficiently repair DNA double strand breaks induced by both high-dose photon and carbon ion radiation. We have shown for the first time that MSCs are relatively resistant to therapeutic carbon ion radiotherapy. Additionally, this form of radiation did not markedly alter the defining stem cell properties or the expression of established surface markers in MSCs.

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“…The radiation response of MSCs has been analyzed both in mouse and human cell samples; several studies using high-dose irradiation have demonstrated that the in-vitro survival of MSCs was considerably higher than that of other bone marrow-derived stem cells and was similar to other rather radio-resistant cell lines [ 64 - 66 ]. Another analysis demonstrated increased radiation resistance of adult human MSCs compared to embryonic stem cells [ 67 ].…”

Section: Influence Of Ionizing Radiation On Mscsmentioning

confidence: 99%

Radio-resistant mesenchymal stem cells: mechanisms of resistance and potential implications for the clinic

et al. 2015

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Mesenchymal stem cells (MSCs) comprise a heterogeneous population of multipotent stromal cells and can be isolated from various tissues and organs. Due to their regenerative potential, they have been subject to intense research efforts, and they may provide an efficient means for treating radiation-induced tissue damage. MSCs are relatively resistant to ionizing radiation and retain their stem cell characteristics even after high radiation doses. The underlying mechanisms for the observed MSC radioresistance have been extensively studied and may involve efficient DNA damage recognition, double strand break repair and evasion of apoptosis. Here, we present a concise review of the published scientific data on the radiobiological features of MSCs. The involvement of different DNA damage recognition and repair pathways in the creation of a radioresistant MSC phenotype is outlined, and the roles of apoptosis, senescence and autophagy regarding the reported radioresistance are summarized. Finally, potential influences of the radioresistant MSCs for the clinic are discussed with respect to the repair and radioprotection of irradiated tissues.

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Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and ionizing radiation

Abstract: These data show that MSCs are highly sensitive to RKIs and combination treatments incorporating IR. Expression analyses suggest that high levels of PDGF receptors may contribute to this effect.

Cited by 13 publications

References 42 publications

Mesenchymal stem cells are sensitive to bleomycin treatment

Mesenchymal stem cells are sensitive to bleomycin treatment

Mesenchymal stem cells are resistant to carbon ion radiotherapy

Radio-resistant mesenchymal stem cells: mechanisms of resistance and potential implications for the clinic

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