Abstract

Microfluidic Chips and Cancer Treatment

John Greenman, Professor of Tumour Immunology, The University Of Hull

Traditionally, development of treatments for diseases such as cancer has started with simple in vitro cell culture models before moving to animals. Unfortunately the majority of therapies fail, with a high associated cost, in large part due to the models neither accurately representing the complex pathophysiology of the disease nor the normal host physiology. Organs are complicated three-dimensional (3D) structures consisting of many different cell types located in a unique spatial arrangement, interweaved with extracellular matrix. In Hull, the approach has been to maintain and “interrogate” human tissue ex vivo in a continuous perfusion model, with the aim of preserving tissue’s 3D in vivo-like structure, retaining the complex cell-to-cell and cell-to-matrix interactions. Human tissues we have studied include: squamous cell carcinoma of the Head and Neck (HNSCC); colorectal carcinoma and normal tissue; ovarian carcinoma; mesothelioma, glioblastoma and heart. The limitations of this approach are the time that tissue can be maintained, and this varies for different tissue/tumour types and for each individual tumour. Up to four days almost no histopathological changes can be observed for all tissues studied and function appears unimpaired. For drug toxicity studies a 9-day incubation period was used on HNSCC to show the additive effect of using multiple chemotherapy drugs on cell death. For studying irradiation effects on colorectal and HNSCC biopsies a 4-day time frame was used; these are measured by immunohistochemical analysis (Ki67, ?H2AX, M30) of the tissue post-irradiation. As expected higher doses or fractionated delivery caused increased cell death. The major challenge now is to undertake the correlative or pseudo-clinical trials in which the tissue-on-chip treatments are compared with the patient response following delivery of the same treatment regimen. An advantage of the lab-on-a-chip approach is that simultaneously other treatments can be tested