title: Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals.
abstract: Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis.
authors.affiliation: 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University , Ithaca, New York.|2 Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst , Amherst, Massachusetts.
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Lynch
authors.affiliation: 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University , Ithaca, New York.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Chiou
authors.affiliation: 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University , Ithaca, New York.
authors.forename: Min Joon
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University , Ithaca, New York.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Marcott
authors.affiliation: 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University , Ithaca, New York.
authors.forename: Praveen V
authors.initials: PV
authors.lastname: Polamraju
authors.affiliation: 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University , Ithaca, New York.
authors.forename: Yeonkyung
authors.initials: Y
authors.lastname: Lee
authors.affiliation: 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University , Ithaca, New York.|3 Kavli Institute at Cornell for Nanoscale Science, Cornell University , Ithaca, New York.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fischbach
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002450:Cell Communication; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010012:Osteogenesis; D015398:Signal Transduction; D013314:Stress, Mechanical; D054457:Tissue Scaffolds / Q000737:chemistry