Mesenchymal stem cells are sensitive to bleomycin treatment

Nicolay, Nils H.; Rühle, Alexander; Perez, Ramon Lopez; Trinh, Thuy; Sisombath, Sonevisay; Weber, Klaus; Ho, Anthony D.; Debus, Jürgen; Saffrich, Rainer; Huber, Peter E.

doi:10.1038/srep26645

Cited by 49 publications

(38 citation statements)

References 50 publications

(66 reference statements)

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“…As hypoxic environment is also known to promote the propagation of tumor initiating cells (TICs) 59,60 , we suspect that the expressional changes of EEA genes may facilitate this process. This is consistent with our finding that drugs like bleomycin and WIKI4 that efficiently eliminate TIC-enriched cell populations 61,62 , cause selective lethality to cancer cell lines that overexpress cluster 1 genes (Fig. 5b).…”

Section: Disscussionsupporting

confidence: 92%

Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability

Jing

Vizeacoumar

Parameswaran

et al. 2018

Preprint

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Can transcriptomic alterations drive the evolution of tumors? We rationalize that expressional changes found in all patients arise earlier in tumor development compared to alterations that occur only in limited subsets of patients. Our analyses of non-mutated genes from the nonamplified regions of the genome of 158 triple negative breast cancer (TNBC) cases identified 219 exclusively expression-altered (EEA) genes that may play important role in TNBC.Phylogenetic analyses of these genes predict a "punctuated burst" of multiple gene upregulation events occurring at early stages of tumor development, followed by minimal subsequent changes later in tumor progression. Remarkably, this punctuated burst of expressional changes is instigated by hypoxia-related molecular events, predominantly in two groups of genes that control chromosomal instability (CIN) and remodel tumor microenvironment (TME). We conclude that alterations in the transcriptome are not stochastic and that early stage hypoxia induces CIN and TME remodeling to permit further tumor evolution.

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Section: Disscussionsupporting

confidence: 92%

Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability

Jing

Vizeacoumar

Parameswaran

et al. 2018

Preprint

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“…Similarly, the data on the influence of bleomycin on MSCs are scarce. Bleomycin treatment was found to reduce viability and proliferation of MSCs, and MSCs were sensitive to the antineoplastic drug compared to differentiated fibroblasts . Additionally, bleomycin exposure resulted in increased apoptosis.…”

Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning

confidence: 98%

“…Functionally, cell migration and adhesion remained unaffected, while the adipogenic differentiation potential was found strongly inhibited. MSCs were reported to efficiently repair DNA double‐strand breaks induced by bleomycin treatment, but the stem cells exhibited very low levels of the inactivating enzyme bleomycin hydrolase that may help to explain the observed sensitivity of MSCs to bleomycin …”

Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning

confidence: 99%

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

Rühle

Huber

Saffrich

et al. 2018

Intl Journal of Cancer

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Chemotherapeutic agents are part of the standard treatment algorithms for many malignancies; however, their application and dosage are limited by their toxic effects to normal tissues. Chemotherapy-induced toxicities can be long-lasting and may be incompletely reversible; therefore, causative therapies for chemotherapy-dependent side effects are needed, especially considering the increasing survival rates of treated cancer patients. Mesenchymal stem cells (MSCs) have been shown to exhibit regenerative abilities for various forms of tissue damage. Preclinical data suggest that MSCs may also help to alleviate tissue lesions caused by chemotherapeutic agents, mainly by establishing a protective microenvironment for functional cells. Due to the systemic administration of most anticancer agents, the effects of these drugs on the MSCs themselves are of crucial importance to use stem cell-based approaches for the treatment of chemotherapy-induced tissue toxicities. Here, we present a concise review of the published data regarding the influence of various classes of chemotherapeutic agents on the survival, stem cell characteristics and physiological functions of MSCs. Molecular mechanisms underlying the effects are outlined, and resulting challenges of MSC-based treatments for chemotherapy-induced tissue injuries are discussed.

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“…S9A). Before CD34 + loading, the eN were exposed to bleomycin (eN-Bleo), as potent drug inducing DNA damage (39). The drug altered hMSC metabolism (30% reduction of activity) (SI Appendix, Fig.…”

Section: Perturbation Of Hsc Behavior By Simulation Of Injury In Engimentioning

confidence: 99%

In vitro biomimetic engineering of a human hematopoietic niche with functional properties

Bourgine

Klein

Paczulla

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

108

107

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In adults, human hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment. Our understanding of human hematopoiesis and the associated niche biology remains limited, due to human material accessibility and limits of existing in vitro culture models. The establishment of an in vitro BM system would offer an experimentally accessible and tunable platform to study human hematopoiesis. Here, we develop a 3D engineered human BM analog by recapitulating some of the hematopoietic niche elements. This includes a bone-like scaffold, functionalized by human stromal and osteoblastic cells and by the extracellular matrix they deposited during perfusion culture in bioreactors. The resulting tissue exhibited compositional and structural features of human BM while supporting the maintenance of HSPCs. This was associated with a compartmentalization of phenotypes in the bioreactor system, where committed blood cells are released into the liquid phase and HSPCs preferentially reside within the engineered BM tissue, establishing physical interactions with the stromal compartment. Finally, we demonstrate the possibility to perturb HSPCs' behavior within our 3D niches by molecular customization or injury simulation. The developed system enables the design of advanced, tunable in vitro BM proxies for the study of human hematopoiesis.

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Mesenchymal stem cells are sensitive to bleomycin treatment

Cited by 49 publications

References 50 publications

Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability

Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

In vitro biomimetic engineering of a human hematopoietic niche with functional properties

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