Microengineered 3D analogues of alveolar tissue for lung regeneration
Scientists of four hDMT partners (University of Twente, Leiden University Medical Center, Maastricht University Medical Centre+ and Erasmus MC) have joined forces to develop an Alveolus-on-Chip model for studies on lung repair. The Lung Foundation Netherlands supports this hDMT project with € 600.000,=. The dynamic functional human model will use alveolar epithelial cells and endothelial cells derived from human induced pluripotent stem cells (hiPSC). The cells are grown on opposite sites of flexible curved membranes.
The project will be presented during the first Netherlands Symposium on Lung Repair and Regeneration, organized by the Netherlands Respiratory Society on November 11, 2016.
Schematic representation of a part of a microwell array with cultured lung epithelial cells: alveolar epithelial type 1 and type 2 cells on the side of the air compartment, and endothelial cells on the opposite side (blood/medium compartment).
The position of the flexible membrane during simulated exhalation and inhalation is indicated.
Chronic lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) are characterized by extensive destruction of lung tissue, and endogenous repair of this tissue is insufficient because of the limited capacity for self-repair of the lung. For end-stage patients with such diseases, lung transplantation is the only remaining option, but the number of donor lungs is limited and the success of lung transplantation is suboptimal. Therefore, there is an urgent need for alternative strategies, such as stem cell therapy, (pharmacological) enhancement of endogenous repair and tissue engineering. Human models are essential for development of such strategies, but current models do not fully capture the complexity of the alveolus.
The project team will develop a new model by growing iPSC-derived lung cells (in collaboration with Christine Mummery, LUMC) on flexible curved membranes allowing exposure to air and fluid flow as well as mechanical forces to simulate the effects of breathing (Figure). The membranes are curved to mimic the sac-like cavities of the alveolus. These features make the model different from previously published Alveolus-on-Chip (1, 2) and Airway-on-Chip models (3). It is anticipated that the model will be valuable as a tool to study lung repair, and to evaluate novel compounds and cell therapies for lung regeneration. Furthermore, by integrating multiple Lung-on-Chip modules we will explore the feasibility of a tissue engineering approach to replace damaged lung tissue.
More information on lung repair
See this recently published review (4).
Project name: Microengineered 3D analogues of alveolar tissue for lung regeneration
Project start date: 1 January 2015
Project end date: 1 July 2019
University of Twente: Thijs Pasman (PhD student), Dimitrios Stamatialis and André Poot (project leader)
Leiden University Medical Center: Sander van Riet (PhD student) and Pieter Hiemstra
Maastricht University: Danielle Baptista (PhD student), Stefan Giselbrecht and Roman Truckenmüller
Erasmus MC: Robbert Rottier and Ismé de Kleer
1. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science. 2010;328(5986):1662-8.
2. Stucki AO, Stucki JD, Hall SR, Felder M, Mermoud Y, Schmid RA, Geiser T, Guenat OT. A lung-on-a-chip array with an integrated bio-inspired respiration mechanism. Lab Chip. 2015;15(5):1302-10.
3. Benam KH, Villenave R, Lucchesi C, Varone A, Hubeau C, Lee HH, Alves SE, Salmon M, Ferrante TC, Weaver JC, Bahinski A, Hamilton GA, Ingber DE. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods. 2016;13(2):151-7.
4. Schilders KA, Eenjes E, van Riet S, Poot AA, Stamatialis D, Truckenmüller R, Hiemstra PS, Rottier RJ. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices. Respir Res. 2016;17(1):44.