A novel device for elimination of cancer cells from blood specimens

Agnes Weth,Werner Baumgartner,Cinzia Donato,Christoph Wolf,Stefan Pirker,Nicola Aceto,Kurt Priesner,Ilona Krol

doi:10.1038/s41598-020-67071-w

Abstract

Circulating tumor cells (CTCs) are derivatives of solid cancerous lesions that detach from the tumor mass and enter the blood circulation. CTCs are considered to be the precursors of metastasis in several cancer types. They are present in the blood of cancer patients as single cells or clusters, with the latter being associated with a higher metastatic potential. Methods to eliminate CTCs from the bloodstream are currently lacking. Here, we took advantage of the lower shear stress-resistance of cancer cells compared to blood cells, and developed a device that can eliminate cancer cells without blood damage. The device consists of an axial pump and a coupled rotating throttle, controllable to prevent local blood flow impairment, yet maintaining a constant shear performance. When processing cancer cells through our device, we observe cancer cell-cluster disruption and viability reduction of single cancer cells, without noticeable effects on human blood cells. When injecting cancer cell-containing samples into tumor-free recipient mice, processed samples fail to generate metastasis. Together, our data show that a selective disruption of cancer cells is possible while preserving blood cells, paving the way towards the development of novel, implantable tools for CTC disruption and metastasis prevention.

Highlights

Circulating tumor cells (CTCs) are derivatives of solid cancerous lesions that detach from the tumor mass and enter the blood circulation
We considered two main parameters to be important for the impact of the shear onto cancer cells as well as onto blood cells: the duration and the magnitude of the applied shear stress
We tested whether our CTC-disruption device was able to destroy cancer cells while preserving the integrity of white blood cells (WBCs) and red blood cells (RBCs)

Summary

Introduction

Circulating tumor cells (CTCs) are derivatives of solid cancerous lesions that detach from the tumor mass and enter the blood circulation. While this is perfectly suited and highly valuable for diagnostic purposes to detect, quantify and characterise CTCs, this system is of limited use for therapeutic approaches aiming to effectively remove CTCs from the blood compartment Blood cells such as erythrocytes, leucocytes and thrombocytes are considered to be well acquainted to liquid shear stress due to their physiological role within the bloodstream. We thought of constructing a non-pumping-pump, i.e. an axial pump coupled to a rotating throttle (referred to here as “CTC-disruption device”) Such a device is controllable in a way that allows operation without impairing the local blood flow, i.e. by adapting the flow rate while applying constant shear performance, which depends on the amplitude and the duration of the shear stress

Methods

Results

Conclusion