Tissue chips - innovative tools for drug development and disease modeling

Abstract

The high rate of failure during drug development is well-known, however recent advances in tissue engineering and microfabrication have contributed to the development of microphysiological systems (MPS), or 'organs-on-chips' that recapitulate the function of human organs. These 'tissue chips' could be utilized for drug screening and safety testing to potentially transform the early stages of the drug development process. They can also be used to model disease states, providing new tools for the understanding of disease mechanisms and pathologies, and assessing effectiveness of new therapies. In the future, they could be used to test new treatments and therapeutics in populations - via clinical trials-on-chips - and individuals, paving the way for precision medicine. Here we will discuss the wide-ranging and promising future of tissue chips, as well as challenges facing their development.

Figure 1

A broad array of tissue chip platforms have been developed. These include (clockwise from top right) a blood-brain barrier (Wikswo lab at Vanderbilt University), cardiac muscle (Parker lab at Harvard), kidney proximal tubule (www.nortis.com), female reproductive tract (DRAPER laboratories), vascularized tumor (George lab at Washington University), skin epidermis (Christiano lab at Columbia), vasculature (George lab at Washington University), liver (Taylor lab at University of Pittsburgh), and lung (www.emulatebio.com). Center image from www.ncats.nih.gov/tissuechip. All images reproduced with permission from the developers.

Figure 2

Neural constructs generated from human embryonic stem cell-derived precursor cells form vascular networks. A) Immunofluorescence for endothelial cells (CD31, green), glial cells (GFAP, red) and nuclei (DAPI, blue) shows multiple cell types growing together. B) Zoom in of the boxed region in A shows association and alignment of a capillary tubule and radially oriented glial cells (arrowheads). Scale bars A-250μm, B-100μm. Figure adapted from Schwartz et al with permission.

Figure 3

The “EVATAR” system, modeling the human reproductive tract. Liver, ovary, ectocervix, uterus and fallopian tube modules are linked by microfluidic channels (left). Ovarian hormone secretion over 28 days in culture with oestradiol and progesterone mimics the human menstrual cycle. Image adapted under a Creative Commons 4.0 license from Xiao et al.

Figure 4

A four-organ chip device from TissUse (Germany). The device consists of two polycarbonate coverplates with a PDMS chip that incorporates intestine (1), liver (2), skin (3) and kidney (4) tissue. Pink represents a surrogate blood flow; yellow represents an excretory flow circuit. Each microphysiological fluid flow circuit is operated by a separate peristaltic micropump. Image adapted under a Creative Commons 3.0 license from Maschmeyer et al.