The idea of creating a splenon-on-a-chip stemmed from the research groups led by Dr. Hernando del Portillo, an ICREA research professor at CRESIB, an ISGlobal research centre, and Dr. Josep Samitier, Director of IBEC and professor at the University of Barcelona. The CRESIB group has been studying the role of the spleen in malaria for several years, while the IBEC group has been investigating the rheological properties of blood including those of malaria-infected blood, to develop diagnostic systems. “Because of ethical and technological limitations, very little progress has been made in the study of the spleen, which is known as the “black box” of the abdominal cavity,” explains del Portillo. To overcome these obstacles, CRESIB and IBEC launched a joint programme to develop a microengineered human splenon-on-a-chip with support from the Spanish government’s EXPLORA project.
As IBEC researcher and co-author of the paper Dr. Antoni Homs explains, “the fluidic system in the spleen is highly complex and has adapted over the course of evolution to selectively filter and destroy old red blood cells, microorganisms, and malaria-infected cells. The spleen filters blood using a unique method, making it “microcirculate” through filtration beds made of splenic red pulp in a special compartment where the hematocrit (percentage of red blood cells) is increased. This facilitates the recognition and destruction of unhealthy cells by specialised macrophages.” Furthermore, the blood in this compartment is only able to travel in one direction and has to pass through interendothelial slits to reach the circulatory system. This constitutes a second, rigorous, control point to ensure the removal of old or unhealthy cells.
Researchers from CRESIB and IBEC, which belong to the Catalan network of research centres, CERCA, mimicked these two test conditions on their micro-sized platform by including two flow-division channels to recreate the closed-fast and open-slow microcirculations of the blood in the spleen. In the slow channel, the blood flows through a pillar matrix that resembles the actual environment where the hematocrit is increased and unhealthy blood is destroyed. The device has been tested with healthy and malaria-infected human red blood cells in studies conducted mainly by predoctoral researchers Luis G. Rigat-Brugarolas (IBEC) and Aleix Elizalde-Torrent (CRESIB/ISGlobal), who are also co-authors of the paper. “Our device should make it easier to study the function of the spleen in the future, and might even provide a flexible platform to screen for potential drugs against malaria and other blood disorders,” says del Portillo.
“Research into organs on chips integrating microfluidics and cell systems is still in its early phases, but it offers holds enormous promise for testing drugs for different diseases in the future,” states Josep Samitier. These 3D devices, by mimicking the tissue–tissue interfaces and unique microenvironments seen in whole living organs, allow new insights into diseases that cannot easily be obtained with conventional animal studies, which are costly and time-consuming. They may also yield results related to humans that animal models cannot predict.
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Reference article: Rigat Brugarolas, L. G., Elizalde Torrent, A., Bernabeu, M., de Niz, M., Martin Jaular, L., Fernandez Becerra, C., Homs Corbera, A., Samitier, J. & del Portillo, H. A. (2014). Functional microengineered model of the human splenon-on-a-chip. Lab Chip, 14, 1715-1724
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To watch a video of the splenon-on-a-chip at work, go to http://www.youtube.com/watch?v=aLuCxj5ojtc
Interviews with Dr. Hernando A. del Portillo and Dr. Josep Samitier:
https://vimeo.com/89099222 (short version)
https://vimeo.com/89093532 (long version)
