Evaluation of function and recovery of adipose-derived stem cells after exposure to paclitaxel

Harris, William M.; Zhang, Ping; Plastini, Michael; Ortiz, Telisha; Kappy, Nikolas; Benites, Jefferson; Alexeev, Edward; Chang, Shaohua; Brockunier, Ross; Carpenter, Jeffrey P.; Brown, Spencer A.

doi:10.1016/j.jcyt.2016.10.010

Cited by 18 publications

(15 citation statements)

References 33 publications

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“…The effects exerted by PTX treatment on MSCs, both in terms of cell proliferation and differentiation ability, have been addressed by several recent papers. Ad-MSCs exposed to PTX lose their multipotent differentiation capability both in in-vitro human Ad-MSC populations and ex-vivo in rat Ad-MSC populations [45]. When PTX-treated hMSCs are induced to undergo adipogenesis they exhibit a 40% reduction in lipid accumulation and adopt fibroblast-like characteristics, including upregulation of fibroblast markers and reduction of stemness markers [46].…”

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

et al. 2017

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BackgroundMesenchymal stem/stromal cells (MSCs) represent an attractive tool for cell-based cancer therapy mainly because of their ability to migrate to tumors and to release bioactive molecules. However, the impact of MSCs on tumor growth has not been fully established. We previously demonstrated that murine MSCs show a strong tropism towards glioblastoma (GBM) brain xenografts and that these cells are able to uptake and release the chemotherapeutic drug paclitaxel (PTX), maintaining their tropism towards the tumor. Here, we address the therapy-relevant issue of using MSCs from human donors (hMSCs) for local or systemic administration in orthotopic GBM models, including xenografts of patient-derived glioma stem cells (GSCs).MethodsU87MG or GSC1 cells expressing the green fluorescent protein (GFP) were grafted onto the striatum of immunosuppressed rats. Adipose hMSCs (Ad-hMSCs), fluorescently labeled with the mCherry protein, were inoculated adjacent to or into the tumor. In rats bearing U87MG xenografts, systemic injections of Ad-hMSCs or bone marrow (BM)-hMSCs were done via the femoral vein or carotid artery. In each experiment, either PTX-loaded or unloaded hMSCs were used. To characterize the effects of hMSCs on tumor growth, we analyzed survival, tumor volume, tumor cell proliferation, and microvascular density.ResultsOverall, the AD-hMSCs showed remarkable tropism towards the tumor. Intracerebral injection of Ad-hMSCs significantly improved the survival of rats with U87MG xenografts. This effect was associated with a reduction in tumor growth, tumor cell proliferation, and microvascular density. In GSC1 xenografts, intratumoral injection of Ad-hMSCs depleted the tumor cell population and induced migration of resident microglial cells. Overall, PTX loading did not significantly enhance the antitumor potential of hMSCs. Systemically injected Ad- and BM-hMSCs homed to tumor xenografts. The efficiency of hMSC homing ranged between 0.02 and 0.5% of the injected cells, depending both on the route of cell injection and on the source from which the hMSCs were derived. Importantly, systemically injected PTX-loaded hMSCs that homed to the xenograft induced cytotoxic damage to the surrounding tumor cells.ConclusionshMSCs have a therapeutic potential in GBM brain xenografts which is also expressed against the GSC population. In this context, PTX loading of hMSCs seems to play a minor role.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0516-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

et al. 2017

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“…Analyses reporting the influence of taxanes on MSCs have produced inconsistent results. While paclitaxel treatment was shown to decrease MSC proliferation in a dose‐dependent manner in some publications, other studies showed uniform reduction in cell numbers with no dose‐dependent effects . The MSCs' proliferative ability seems strongly impaired by paclitaxel treatment, although the stem cells remained metabolically viable even after exposure to high doses .…”

Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning

confidence: 99%

“…The MSCs' proliferative ability seems strongly impaired by paclitaxel treatment, although the stem cells remained metabolically viable even after exposure to high doses . The level of apoptosis induction in paclitaxel‐treated MSCs has also been subject to controversy, with several datasets demonstrating slightly or strongly increased apoptosis, while only one publication reported no increase of apoptotic cells . On a molecular level, up‐regulation of TNF‐α after paclitaxel treatment was found associated with increased apoptosis in MSCs .…”

Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning

confidence: 99%

“…Additionally, it has been demonstrated that paclitaxel resulted in a significant increase of premature senescence in MSCs, explaining the stem cells' observed preservation of viability despite a strong reduction in proliferation . Contrary to alkylating agents, methotrexate and arsenic trioxide, paclitaxel led to a long‐lasting suppression of cell growth after withdrawal of the drug . Paclitaxel treatment had no influence on the regulation of the P‐glycoprotein in MSCs that plays an important role in the mediation of chemotherapy resistance .…”

Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning

confidence: 99%

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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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“…Cell viability was evaluated by MTT [3 (4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide] colorimetric assay [30]. After 24 h experiment, 100 µL of MTT was added to each well, and then, after 3 h the formazan crystals formed were dissolved in DMSO (50 µL).…”

Section: Cell Viability Studiesmentioning

confidence: 99%

A novel ultradeformable liposomes of Naringin for anti-inflammatory therapy

Pleguezuelos-Villa

Mir-Palomo

Dı́ez-Sales

et al. 2018

Colloids and Surfaces B: Biointerfaces

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The article has 4636 words including ackwonledgment and references. The abstract has 127 words. There are 5 figures and 2 tables. Highlights Nanovesicles were small in size and monodispersed independently of the NA concentration. No citotoxity effects were observed in 3T3 fibroblasts treated with ultradeformable liposomes. Ultradeformable liposomes have the ability to reduce skin inflammation. Graphical abstract AbstractUltradeformable liposomes were formulated using naringin (NA), a flavanone glycoside, at different concentrations (3, 6 and 9 mg/mL). Nanovesicles were small size (~100 nm), regardless of the NA concentration used, and monodisperse (PI < 0.30). All formulations showed a high entrapment efficiency (~88%) and a highly negative zeta potential (around -30 mV). The selected formulations were highly biocompatible as confirmed by in vitro studies using 3T3 fibroblasts.In vitro assay showed that the amounts (%) of NA accumulated in the epidermis (~ 10%) could explain the anti-inflammatory properties of ultradeformable liposomes. In vivo studies confirmed the higher effectiveness of ultradeformable liposomes respect to betamethasone cream and NA dispersion in reducing skin inflammation in mice. Overall, it can conclude that NA ultradeformable liposomes can be considered as a promising formulation for the treatment of skin inflammatory diseases.

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Evaluation of function and recovery of adipose-derived stem cells after exposure to paclitaxel

Cited by 18 publications

References 33 publications

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

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

A novel ultradeformable liposomes of Naringin for anti-inflammatory therapy

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