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A Novel Approach to Targeted Oncologic Therapy - Co-Culture Viability of Polymer Prodrug Conjugation to Mesenchymal Stem Cells
*Kaitlyn Wong, MD, *N. Panzarino, MS, *S. McRae, B.S., R. Arenas, MD, *S. Schneider, PhD, *T. Emrick, PhD
Baystate Medical Center, Springfield, MA
OBJECTIVE: Conjugation of chemotheraputic agents or polymer prodrugs to tumor homing cells, such as Mesenchymal Stem Cells (MSCs), could provide a vehicle for actively targeted delivery of these drugs. Our objective was to determine if MSCs can be engineered to deliver drugs to tumors cells without affecting viability or altering their migratory capabilities following drug conjugation to cells in vitro.
DESIGN: Basic Science.
SETTING: In vitro
PARTICIPANTS: 1) Transgenic mice that spontaneously develop GIST, 2) NOD-SCID-IL-2R?-null mice with subcutaneously implanted GIST-T1 xenografts.
INTERVENTIONS: MSCs were conjugated to either a doxorubicin polymer prodrug, a rhodamine-containing polymer, or free doxorubicin in a 10 uM solution for 15 minutes. The conjugated MSCs were then co-cultured with T-cells or breast cancer cells. Viability was assessed through the use of a Vi-cell counter. The migratory ability of prodrug loaded MSCs was assed by an in vitro migration assay.
MAIN OUTCOME MEASURES: Cell viability and migration.
RESULTS: T-cell viability was reduced and breast cancer showed senescence of growth when co-cultured with MSCs conjugated to free doxorubicin. T-cells and breast cancer cells co-cultured with MSCs conjugated to both rhodamine polymer and the doxorubicin polymer prodrug had similar viability when compared to controls. Prodrug loaded MSCs also displayed intact migratory ability in vitro.
CONCLUSIONS: MSCs conjugated to doxorubicin were resistant to death-inducing effects of the drug. However, over time MSCs released doxorubicin, resulting in a time dependent decreased viability of neighboring T-cells and senescence of growth of breast cancer cells. MSCs loaded with doxorubicin prodrugs maintained their migratory capacity in vitro. Future work will be focused on how to release the drug upon successful delivery to the target in vivo.
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