Stem Cell Implants for Cancer Therapy: TRAIL-Expressing Mesenchymal Stem Cells Target Cancer Cells In Situ.
10.4048/jbc.2012.15.3.273
- Author:
Michaela R REAGAN
1
;
F Philipp SEIB
;
Douglas W MCMILLIN
;
Elizabeth K SAGE
;
Constantine S MITSIADES
;
Sam M JANES
;
Irene M GHOBRIAL
;
David L KAPLAN
Author Information
1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
- Publication Type:In Vitro ; Original Article
- Keywords:
Breast neoplasms;
Mesenchymal stem cells;
Tissue engineering;
Tissue therapy;
TNF-related apoptosis-inducing ligand
- MeSH:
Adipose Tissue;
Animals;
Breast Neoplasms;
Doxycycline;
Liver;
Lung;
Mesenchymal Stromal Cells;
Mice;
Necrosis;
Neoplasm Metastasis;
Seeds;
Silk;
Stem Cells;
Stromal Cells;
Tissue Engineering;
Tissue Therapy;
TNF-Related Apoptosis-Inducing Ligand;
Tumor Burden;
Veins
- From:Journal of Breast Cancer
2012;15(3):273-282
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Tumor-specific delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an apoptosis-inducing peptide, at effective doses remains challenging. Herein we demonstrate the utility of a scaffold-based delivery system for sustained therapeutic cell release that capitalizes on the tumor-homing properties of mesenchymal stem cells (MSCs) and their ability to express genetically-introduced therapeutic genes. METHODS: Implants were formed from porous, biocompatible silk scaffolds seeded with full length TRAIL-expressing MSCs (FLT-MSCs). under a doxycycline inducible promoter. In vitro studies with FLT-MSCs demonstrated TRAIL expression and antitumor effects on breast cancer cells. Next, FLT-MSCs were administered to mice using three administration routes (mammary fat pad co-injections, tail vein injections, and subcutaneous implantation on scaffolds). RESULTS: In vitro cell-specific bioluminescent imaging measured tumor cell specific growth in the presence of stromal cells and demonstrated FLT-MSC inhibition of breast cancer growth. FLT-MSC implants successfully decreased bone and lung metastasis, whereas liver metastasis decreased only with tail vein and co-injection administration routes. Average tumor burden was decreased when doxycycline was used to induce TRAIL expression for co-injection and scaffold groups, as compared to controls with no induced TRAIL expression. CONCLUSION: This implant-based therapeutic delivery system is an effective and completely novel method of anticancer therapy and holds great potential for clinical applications.
