Microfluidic Graft-Versus-Host Disease Tissue Model

Microfluidic Graft-versus-Host Disease Tissue Model

Karolina Konior¹, Wenting Zhang¹, Yexin Gu¹, Yi Hao¹, Zhehuan Chen¹, Jenny Zilberbeg², Woo Y. Lee¹

¹Depertment of Chemical Engineering and Materials Science, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, NJ 07030

²Research Department, Hackensack University Medical Center, 40 Prospect Ave, Hackensack, NJ, 07601

Abstract

            It is challenging to determine prior to allogenic blood and marrow transplantation (BMT) whether a patient will develop effects of transplant rejection. After allogenic BMT, nearly 50% of patients currently experience acute graft-versus-host disease (GVHD), characterized by damage to gastrointestinal (GI) tract, skin, and liver tissues elicited by donor T cells. A microfluidic GVHD tissue model is proposed as a means of replicating ex vivo GVHD using patient intestinal epithelial cells and donor T cells for diagnostic screening of potential patient-donor mismatch. As initial steps toward this long goal, we used a microfluidic device to: (1) culture and maintain primary murine intestinal epithelial cells (IECs) and (2) assess the device's capability in supporting the circulation and interaction of primary murine T cells with the IECs.  For the IEC culture, polycaprolactone nanofiber mesh was used to maintain the long-term viability of IECs since primary IECs cannot be kept viable during conventional culture. With the use of nanofiber mesh, IECs were able to develop into a confluent layer and exhibit cobblestone morphology while remaining viable in the culture device.  After IECs became confluent, murine primary T cells were introduced and circulated through the culture device.  T cells were activated by IECs, resulting in the increased viability of T cells. These results suggest that the device can be used to: (1) support long-term culture of primary murine IECs through the enabling use of PCL/collagen nanofiber mesh and (2) circulate and maintain viable T cells without entrapment. With this initial basis, we plan to further optimize the use of the device in replicating the ex vivo alloreaction of T cells initially using established murine models and later using biospecimens obtained from patient-donor pairs.