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 language | English |
|---|---|
| Pages (from-to) | 1687-1695 |
| Number of pages | 9 |
| Journal | Cytotherapy |
| Volume | 17 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2015 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84947569539&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947569539&partnerID=8YFLogxK
U2 - 10.1016/j.jcyt.2015.09.005
DO - 10.1016/j.jcyt.2015.09.005
M3 - Article
VL - 17
SP - 1687
EP - 1695
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
IS - 12
ER -