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

Valentina Cocce, Luigi Balducci, Maria Laura Falchetti, Luisa Pascucci, Emilio Ciusani, Anna Teresa Brini, Francesca Sisto, Giovanna Piovani, Giulio Alessandri, Eugenio Agostino Parati, Laura Cabeza, Augusto Pessina

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)1578-1585
Number of pages8
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 24 2017

Cite this

Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles. / Cocce, Valentina; Balducci, Luigi; Falchetti, Maria Laura; Pascucci, Luisa; Ciusani, Emilio; Brini, Anna Teresa; Sisto, Francesca; Piovani, Giovanna; Alessandri, Giulio; Parati, Eugenio Agostino; Cabeza, Laura; Pessina, Augusto.

In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 17, No. 11, 24.11.2017, p. 1578-1585.

Research output: Contribution to journalArticle

Cocce, Valentina ; Balducci, Luigi ; Falchetti, Maria Laura ; Pascucci, Luisa ; Ciusani, Emilio ; Brini, Anna Teresa ; Sisto, Francesca ; Piovani, Giovanna ; Alessandri, Giulio ; Parati, Eugenio Agostino ; Cabeza, Laura ; Pessina, Augusto. / Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles. In: Anti-Cancer Agents in Medicinal Chemistry. 2017 ; Vol. 17, No. 11. pp. 1578-1585.
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abstract = "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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T1 - Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles.

AU - Cocce, Valentina

AU - Balducci, Luigi

AU - Falchetti, Maria Laura

AU - Pascucci, Luisa

AU - Ciusani, Emilio

AU - Brini, Anna Teresa

AU - Sisto, Francesca

AU - Piovani, Giovanna

AU - Alessandri, Giulio

AU - Parati, Eugenio Agostino

AU - Cabeza, Laura

AU - Pessina, Augusto

PY - 2017/11/24

Y1 - 2017/11/24

N2 - 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.

AB - 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.

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

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U2 - 10.2174/1871520617666170327113932

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JO - Anti-Cancer Agents in Medicinal Chemistry

JF - Anti-Cancer Agents in Medicinal Chemistry

SN - 1871-5206

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