Investigating the role of fluid shear stress in bone metastasis: the proliferation of co-cultured hMSCs/MDAPCa2b cells under dynamic culturing.

Abstract: We investigated the potential correlation between the fluid shear stress and the proliferation of bone prostate cancer cells on the surface of nanoclay-based scaffolds in a perfusion bioreactor. Human mesenchymal stem cells (hMSCs) were seeded on the scaffolds to initiate bone growth. After 23 days, prostate cancer cells (MDAPCa2b) were cultured on top of the osteogenically differentiated hMSCs. The scaffolds were separated into two groups subjected to two distinct conditions: (i) static (no flow); and (ii) dynamic (with flow) conditions to recapitulate bone metastasis of prostate cancer. Based on measured data, Computational Fluid Dynamics (CFD) models were constructed to determine the velocity and shear stress distributions on the scaffold surface. Our experimental results show distinct differences in the growth pattern of hMSCs and MDAPCa2b cells between the static and dynamic conditions. Our computational results further suggest that the dynamic flow leads to drastic change in cell morphology and tumorous distribution. Our work points to a strong correlation between tumor growth and local interstitial flows in bones.