Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model

Pessina, Augusto; Leonetti, Carlo; Artuso, Simona; Benetti, Anna; Dessy, Enrico; Pascucci, Luisa; Passeri, Daniela; Orlandi, Augusto; Berenzi, Angiola; Bonomi, Andrea; Coccè, Valentina; Ceserani, Valentina; Ferri, Luca; Dossena, Marta; Mazzuca, Pietro; Ciusani, Emilio; Ceccarelli, Piero; Caruso, Arnaldo; Portolani, Nazario; Sisto, Francesca; Parati, Eugenio; Alessandri, Giulio

doi:10.1186/s13046-015-0200-3

Cited by 31 publications

(30 citation statements)

References 48 publications

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“…PTX was purchased from Adipogen (Vinci-Biochem, Italy). Priming of ASCs was performed as previously described [ 46 ]. Briefly, ASCs were incubated for 24h with different concentrations of PTX (from 10nM to 10μM).…”

Section: Methodsmentioning

confidence: 99%

“…Incorporation and subsequently release of PTX from ASCs was assessed by HPLC analysis, using a standard sample of PTX in PBS. The latter showed a peak of identical retention time of PTX eluted from the PTX-loaded ASC-conditioned medium [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

“…Absorbance as optical density units was determined at 570 nm by a microplate reader (Sunrise TECAN, LabX, Midland, ON, Canada). The inhibitory concentration (IC 50 ) were determined according to the Reed and Muench formula [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

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Adipose-derived stem cell-mediated paclitaxel delivery inhibits breast cancer growth

Artuso

D’Angelo²,

Porru

et al. 2018

PLoS ONE

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Breast cancer represents the main malignancy in women and autologous fat grafting is a diffuse procedure in the management of post-surgical breast defects causing patients’ psychosocial problems, with high costs for the public health. Recently, beneficial effects of fat grafting during post-surgical breast reconstruction have been amplified from the enrichment with human adipose-derived stem cells (ASCs) present in the stromal vascular fraction (SVF) of adult adipose tissue isolated during intraoperatory procedures. The major concern about the ASC enrichment during post-surgery breast reconstruction depends on their potential ability to release growth factors and hormones that can promote proliferation of residual or quiescent cancer cells, with the risk of de novo cancer development or recurrence. The recent description that adult stem cells primed in vitro may be vehicle for anti-cancer drug delivery offers a new vision concerning the role of ASCs in breast reconstruction after cancer surgery. Paclitaxel (PTX) is a chemotherapeutic agent acting as a microtubule-stabilizing drug inhibiting cancer cell mitotic activity. We optimized PTX loading and release in cultured ASCs and then analyzed the effects of PTX-loaded ASCs and their conditioned medium on CG5 breast cancer survival, proliferation and apoptosis in vitro, and inCG5 xenograft in vivo. We documented that ASCs can uptake and release PTX in vitro, with slight cytotoxic effects. Interestingly, PTX-loaded ASCs in co-culture, as well as conditioned medium alone, inhibited CG5 cell proliferation and survival in vitro and xenograft tumor growth in vivo. The antitumor effect of PTX-loaded ASCs may offer a new perspective concerning the use of ASCs during breast reconstruction becoming an additional local preventive chemotherapeutic agent against tumor recurrence. However, further experiments in vitro and in vivo are needed to collect more evidence confirming the efficacy and safety in cancer patients.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Adipose-derived stem cell-mediated paclitaxel delivery inhibits breast cancer growth

Artuso

D’Angelo²,

Porru

et al. 2018

PLoS ONE

Self Cite

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“…In contrast to other studies, in which MSCs deliver an enzyme necessary to convert a prodrug into a pharmacologically active drug, primed MSCs do not need to be genetically modified. The loaded MSCs release their cytotoxic payload packed in exosomes at the sites of tumour or metastatic growth [123,124]. Overall, MSCs can be loaded with a broad spectrum of anti-cancer agents [125].…”

Section: The Potential Impact Of Mscs On Anti-cancer Therapiesmentioning

confidence: 99%

The future of mesenchymal stem cell-based therapeutic approaches for cancer – From cells to ghosts

Mohr

Zwacka

2018

Cancer Letters

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Mesenchymal stem cells (MSCs) are multipotent stromal cells which can differentiate into a variety of cell types including osteoblasts, adipocytes and chondrocytes. They are normally resident in adipose tissue, bone marrow and the umbilical cord, but can also be found in other tissues and are known to be recruited to sites of wound healing as well as growing tumours. The therapeutic potential of MSCs has been explored in a number of phase I/II and III clinical trials, of which several were targeted against graft-versus-host disease and to support engraftment of haematopoietic stem cells (HSCs), but currently only very few in the oncology field. There are now three clinical trials either ongoing or recruiting patients that use MSCs to treat tumour disease. In these, MSCs target gastrointestinal, lung and ovarian cancer, respectively. The first study uses MSCs loaded with a HSV-TK expression construct under the control of the CCL5 promoter, and has recently reported successful completion of Phase I/II. While no adverse side effects were seen during this study, no outcomes with respect to therapeutic benefits have been published. The other clinical trials targeting lung and ovarian cancer will be using MSCs expressing cytokines as therapeutic payload. Despite these encouraging early steps towards their clinical use, many questions are still unanswered regarding the biology of MSCs in normal and pathophysiological settings. In this review, in addition to summarising the current state of MSC-based therapeutic approaches for cancer, we will describe the remaining questions, obstacles and risks, as well as novel developments such as MSC-derived nanoghosts.

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“…Additionally, thanks to their proven ability to migrate and engraft in the stroma of several tumors [9], MSCs have been used in preclinical and clinical studies as carriers of antitumor drugs with the aim of enhancing their selective accumulation at the tumor site. In 2002, Studeny et al firstly proposed MSCs as carrier cells for gene therapy [10]; at present, several studies have been published reporting MSCs as effective delivery vehicles of anticancer agents, such as pro-apoptotic molecules, chemotherapeutic drugs and oncolytic viruses [11][12][13][14][15][16][17][18][19][20]. In addition, it has been extensively demonstrated that MSCs can internalize and deliver nanoparticles loaded with therapeutic agents [21][22][23][24][25], including chemotherapeutic drugs and photosensitizers (PS) for photodynamic therapy (PDT) applications [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal cells mediated delivery of photoactive nanoparticles inhibits osteosarcoma growth in vitro and in a murine in vivo ectopic model

Lenna

Bellotti

Duchi

et al. 2020

J Exp Clin Cancer Res

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Background: Osteosarcoma (OS) is an aggressive malignant neoplasm that still suffers from poor prognosis in the case of distal metastases or occurrence of multi-drug resistance. It is therefore crucial to find novel therapeutic options able to go beyond these limitations and improve patients' survival. The objective of this study is to exploit the intrinsic properties of mesenchymal stromal cells (MSCs) to migrate and infiltrate the tumor stroma to specifically deliver therapeutic agents directly to cancer cells. In particular, we aimed to test the efficacy of the photoactivation of MSCs loaded with nanoparticles in vitro and in a murine in vivo ectopic osteosarcoma model. Methods: AlPcS 4 @FNPs were produced by adding tetra-sulfonated aluminum phthalocyanine (AlPcS 4) to an aqueous solution of positively charged poly-methyl methacrylate core-shell fluorescent nanoparticles (FNPs). The photodynamic therapy (PDT) effect is achieved by activation of the photosensitizer AlPcS 4 in the near-infrared light with an LED source. Human MSCs were isolated from the bone marrow of five donors to account for inter-patients variability and used in this study after being evaluated for their clonogenicity, multipotency and immunophenotypic profile. MSC lines were then tested for the ability to internalize and retain the nanoparticles, along with their migratory properties in vitro. Photoactivation effect was evaluated both in a monolayer (2D) co-culture of AlPcS 4 @FNPs loaded MSCs with human OS cells (SaOS-2) and in tridimensional (3D) multicellular spheroids (AlPcS 4 @FNPs loaded MSCs with human OS cells, MG-63). Cell death was assessed by AnnexinV/PI and Live&Dead CalceinAM/EthD staining in 2D, while in the 3D co-culture, the cell killing effect was measured through ATP content, CalceinAM/EthD staining and TEM imaging. We also evaluated the effectiveness of AlPcS 4 @FNPs loaded MSCs as delivery systems and the ability of the photodynamic treatment to kill cancer cells in a subcutaneous mouse model of OS by bioluminescence imaging (BLI) and histology. Results: MSCs internalized AlPcS 4 @FNPs without losing or altering their motility and viability in vitro. Photoactivation of AlPcS 4 @FNPs loaded MSCs induced high level of OS cells death in the 2D co-culture. Similarly, in the 3D co-culture (MSCs:OS ratios 1:1 or 1:3), a substantial decrease of both MSCs and OS cells viability was observed. Notably, when increasing the MSCs:OS ratio to 1:7, photoactivation still caused more than 40% cells death. When tested in an in vivo ectopic OS model, AlPcS4@FNPs loaded MSCs were able to decrease OS growth by 68% after two cycles of photoactivation.

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Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model

Cited by 31 publications

References 48 publications

Adipose-derived stem cell-mediated paclitaxel delivery inhibits breast cancer growth

Adipose-derived stem cell-mediated paclitaxel delivery inhibits breast cancer growth

The future of mesenchymal stem cell-based therapeutic approaches for cancer – From cells to ghosts

Mesenchymal stromal cells mediated delivery of photoactive nanoparticles inhibits osteosarcoma growth in vitro and in a murine in vivo ectopic model

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