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Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles

[ Vol. 17 , Issue. 11 ]

Author(s):

Valentina Cocce, Luigi Balducci, Maria L. Falchetti, Luisa Pascucci, Emilio Ciusani, Anna T. Brini, Francesca Sisto, Giovanna Piovani, Giulio Alessandri, Eugenio Parati, Laura Cabeza and Augusto Pessina*   Pages 1578 - 1585 ( 8 )

Abstract:


Background: A new tool for the drug delivery is based on the use of Mesenchymal Stromal Cells (MSCs) loaded in vitro with anti-cancer drugs. Unfortunately, the restricted lifespan of MSCs represents a significant limitation to produce them in high amounts and for long time studies. Immortalized MSCs from adipose tissue (hASCs) have been generated as good source of cells with stable features. These cells could improve the development of standardized procedures for both in vitro and preclinical studies. Furthermore they facilitate procedures for preparing large amounts of secretome containing microvesicles (MVs).

Method: We used human adipose tissue derived MSCs immortalized with hTERT+SV40 (TS) genes and transfected with GFP (hASCs-TS/GFP+). This line was investigated for its ability to uptake and release anticancer drugs. Microvesicles associated to paclitaxel (MVs/PTX) were isolated, quantified, and tested on pancreatic cancer cells.

Results: The line hASCs-TS/GFP+ maintained the main mesenchymal characters and was able to uptake and release, in active form, both paclitaxel and gemcitabine. From paclitaxel loaded hASCs-TS/GFP+ cells were isolated microvesicles in sufficient amount to inhibit “in vitro” the proliferation of pancreatic tumor cells.

Conclusion: Our study suggests that human immortalized MSCs could be used for a large scale production of cells for mediated drug delivery. Moreover, the secretion of drug-associated MVs could represent a new way for producing new drug formulation by “biogenesis”. In the context of the “advanced cell therapy procedure”, the MVs/PTX production would use less resource and time and it could possibly contribute to simplification of GMP procedures.

Keywords:

Mesenchymal stromal cells, immortalized MSCs, paclitaxel, gemcitabine, microvesicles, drug delivery.

Affiliation:

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Medestea Research and Production Laboratories, Consorzio CARSO, Bari, CNR-Institute of Cell Biology and Neurobiology, via del Fosso di Fiorano, 64-00143, Rome, Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Laboratory of Clinical Pathology and Neurogenetic Medicine, Fondazione IRCCS Neurological Institute Carlo Besta, Via Celoria 11, 20133 Milan, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, IRCCS Neurological Institute C. Besta, via Celoria 11, 20133 Milan, Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, IRCCS Neurological Institute C. Besta, via Celoria 11, 20133 Milan, Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS University of Granada, Granada, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan

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