Effect of canine mesenchymal stromal cells loaded with paclitaxel on growth of canine glioma and human glioblastoma cell lines

Bonomi, Andrea; Ghezzi, E; Pascucci, Luisa; Aralla, Marina; Ceserani, Valentina; Pettinari, Letizia; Coccè, Valentina; Guercio, Annalisa; Alessandri, Giulio; Parati, Eugenio; Brini, A.T.; Zeira, Offer; Pessina, Augusto

doi:10.1016/j.tvjl.2017.05.005

Cited by 20 publications

(12 citation statements)

References 26 publications

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“…[24][25][26] Recent in vitro studies have shown that after MSC uptake, the active form of Ptx can be released from MSC Ptx via the Pgp system or via membrane microvesicles, giving MSCs their strong antitumor activity. 14,27 However, cell dysfunction after Ptx priming, mechanical filtration of circulating MSCs, and the bloodbrain barrier make convenient systematic injection methods challenging, including injections into the tail vein, femoral vein, and carotid artery. This is because few MSCs engraft at the brain-tumor site.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stem cells loaded with paclitaxel–poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Wang¹,

J²,

Ouyang³

et al. 2018

IJN

100

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BackgroundMesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment.PurposeThe objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats.MethodsPtx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection.ResultsThe optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone.ConclusionBased on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.

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Section: Discussionmentioning

confidence: 99%

“…The active form of Ptx and its antitumor effect has been investigated in MSC Ptx. 6,27 One study reported that about 60% of Ptx was released from human gingival MSCs in 48 hours and the microtubule-bound Ptx remained in the cells. 33 In the present study, we found that about 25% of Ptx was released from MSC Ptx.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells loaded with paclitaxel–poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Wang¹,

J²,

Ouyang³

et al. 2018

IJN

100

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“… Bonomi et al (2017a) in their work used MSCs from two sources: dog adipose tissue and bone marrow, to study MSCs-PTX antitumor activity on human glioma cells (T98G and U87MG). The investigation once again showed the pronounced antitumor effect of MSCs-PTX and opens new perspectives for oncological disease therapy not only in humans but also in animals ( Bonomi et al, 2017a ).…”

Section: Mscs Primed With Anticancer Drugsmentioning

confidence: 99%

Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

et al. 2018

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Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs), which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.

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“…In cells of mesenchymal origin, the switch to a quiescence state following paclitaxel exposure has been already described [73]. However, studies mainly focused on mesenchymal stem cells and on the possibility to use paclitaxel resistant cells as a reservoir of active compound (as a Trojan horse) for local-regional drug delivery [74]. Very recently, Coccè and co-workers, demonstrated that gingival mesenchymal stem cells treated with paclitaxel release vesicle containing an anti-cancer secretome in addition to free paclitaxel [75].…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Targeting Tumor Cells and Cancer-Associated Fibroblasts with a Paclitaxel-Hyaluronan Bioconjugate: in vitro Evaluation in Non-Melanoma Skin Cancer

Bellei

Caputo

Migliano

et al. 2020

Preprint

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Abstract Background: Cancers are complex organs which encompass not only the tumor cells but also cells within the surrounding stroma. Such cells, mainly cancer associated fibroblasts (CAFs) and immune infiltrating cells, facilitate many aspects of cancer development providing a structural and supportive framework rich of bioactive compounds. So far, there are emerging studies proposing the combination of conventional anti-cancer therapy, directed against neoplastic cells, to molecules targeting tumor microenviroment. Methods: The study was designed to evaluated the pharmacological properties of the anti-tumor agent paclitaxel conjugated to hyaluronic acid (HA) on non-melanoma skin cancer (NMSC) and on the surronding dermal fibroblasts. This molecule, named Oncofid-P20 (Onco-P20), targets preferentially cells expressing high level of CD44, the natural ligand of HA.Results: Consistent with paclitaxel’s mechanism of action involving interferences with the normal breackdown of microtubules during cell division, highly sensible carcinoma cells underwent rapidly to apoptotic cell death. Interestingly, less sensible cells such as dermal fibroblasts resisted to the Onco-P20 treatment and experirenced a senescent-like status characterized by morphological change, decreaded proliferation, and significant modification of the gene espression profile. Onco-P20-treated fibroblasts lowered growth factors production, down-modulate Wnt signal pathway and acquired a pro-inflammatory profile. Independently to the direct exposure to taxol, in presence of Onco-P20-treated fibroblasts or their conditioned medium, carcinoma cells reduced the proliferation rate. Similar to NHF, fibroblasts isolated from skin cancer tumor lesion or from tissue adjacent to the tumor acquired an anti-neoplastic activity under Oncofid-P20 treatment.Conclusion: Collectively, our data demonstrated that Onco-P20, exerting both a direct and a NHF-mediated indirect paracrine effect on carcinoma cells, is a good candidate for an innovative therapy alternative to surgery for treatment of NMSC.

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Effect of canine mesenchymal stromal cells loaded with paclitaxel on growth of canine glioma and human glioblastoma cell lines

Cited by 20 publications

References 26 publications

Mesenchymal stem cells loaded with paclitaxel–poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Mesenchymal stem cells loaded with paclitaxel–poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

Simultaneous Targeting Tumor Cells and Cancer-Associated Fibroblasts with a Paclitaxel-Hyaluronan Bioconjugate: in vitro Evaluation in Non-Melanoma Skin Cancer

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Effect of canine mesenchymal stromal cells loaded with paclitaxel on growth of canine glioma and human glioblastoma cell lines

Cited by 20 publications

References 26 publications

Mesenchymal stem cells loaded with paclitaxel&ndash;poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Mesenchymal stem cells loaded with paclitaxel&ndash;poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

Simultaneous Targeting Tumor Cells and Cancer-Associated Fibroblasts with a Paclitaxel-Hyaluronan Bioconjugate: in vitro Evaluation in Non-Melanoma Skin Cancer

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Product

Resources

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Mesenchymal stem cells loaded with paclitaxel–poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Mesenchymal stem cells loaded with paclitaxel–poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy