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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.
Anti-Cancer Agents in Medicinal Chemistry
Title:Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles
Volume: 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*
Affiliation:
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan,Italy
Keywords: Mesenchymal stromal cells, immortalized MSCs, paclitaxel, gemcitabine, microvesicles, drug delivery.
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.
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Cite this article as:
Cocce Valentina, Balducci Luigi , Falchetti L. Maria , Pascucci Luisa , Ciusani Emilio , Brini T. Anna , Sisto Francesca , Piovani Giovanna, Alessandri Giulio, Parati Eugenio , Cabeza Laura and Pessina Augusto *, Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (11) . https://dx.doi.org/10.2174/1871520617666170327113932
DOI https://dx.doi.org/10.2174/1871520617666170327113932 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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