Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells

Arianna Bonomi, Valeria Sordi, Erica Dugnani, Valentina Ceserani, Marta Dossena, Valentina Coccè, Loredana Cavicchini, Emilio Ciusani, Gianpietro Bondiolotti, Giovanna Piovani, Luisa Pascucci, Francesca Sisto, Giulio Alessandri, Lorenzo Piemonti, Eugenio Parati, Augusto Pessina

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background aims: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. Methods: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. Results: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. Conclusions: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection.

Original languageEnglish
Pages (from-to)1687-1695
Number of pages9
JournalCytotherapy
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

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gemcitabine
Mesenchymal Stromal Cells
Pancreatic Neoplasms
Neoplasms
In Vitro Techniques
Pancreatic Carcinoma
Pharmaceutical Preparations

Keywords

  • Drug delivery
  • Gemcitabine
  • MSCs
  • Pancreatic adenocarcinoma

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Oncology
  • Genetics(clinical)
  • Transplantation
  • Cancer Research
  • Cell Biology

Cite this

Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells. / Bonomi, Arianna; Sordi, Valeria; Dugnani, Erica; Ceserani, Valentina; Dossena, Marta; Coccè, Valentina; Cavicchini, Loredana; Ciusani, Emilio; Bondiolotti, Gianpietro; Piovani, Giovanna; Pascucci, Luisa; Sisto, Francesca; Alessandri, Giulio; Piemonti, Lorenzo; Parati, Eugenio; Pessina, Augusto.

In: Cytotherapy, Vol. 17, No. 12, 01.12.2015, p. 1687-1695.

Research output: Contribution to journalArticle

Bonomi, A, Sordi, V, Dugnani, E, Ceserani, V, Dossena, M, Coccè, V, Cavicchini, L, Ciusani, E, Bondiolotti, G, Piovani, G, Pascucci, L, Sisto, F, Alessandri, G, Piemonti, L, Parati, E & Pessina, A 2015, 'Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells', Cytotherapy, vol. 17, no. 12, pp. 1687-1695. https://doi.org/10.1016/j.jcyt.2015.09.005
Bonomi, Arianna ; Sordi, Valeria ; Dugnani, Erica ; Ceserani, Valentina ; Dossena, Marta ; Coccè, Valentina ; Cavicchini, Loredana ; Ciusani, Emilio ; Bondiolotti, Gianpietro ; Piovani, Giovanna ; Pascucci, Luisa ; Sisto, Francesca ; Alessandri, Giulio ; Piemonti, Lorenzo ; Parati, Eugenio ; Pessina, Augusto. / Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells. In: Cytotherapy. 2015 ; Vol. 17, No. 12. pp. 1687-1695.
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abstract = "Background aims: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. Methods: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. Results: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. Conclusions: The use of MSCs as a {"}trojan horse{"} can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection.",
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T1 - Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells

AU - Bonomi, Arianna

AU - Sordi, Valeria

AU - Dugnani, Erica

AU - Ceserani, Valentina

AU - Dossena, Marta

AU - Coccè, Valentina

AU - Cavicchini, Loredana

AU - Ciusani, Emilio

AU - Bondiolotti, Gianpietro

AU - Piovani, Giovanna

AU - Pascucci, Luisa

AU - Sisto, Francesca

AU - Alessandri, Giulio

AU - Piemonti, Lorenzo

AU - Parati, Eugenio

AU - Pessina, Augusto

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background aims: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. Methods: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. Results: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. Conclusions: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection.

AB - Background aims: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. Methods: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. Results: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. Conclusions: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection.

KW - Drug delivery

KW - Gemcitabine

KW - MSCs

KW - Pancreatic adenocarcinoma

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