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A7634 - Lung Bioengineering and Direct Pulmonary Cell Therapy Using a Novel Airway Spray Device
Author Block: S. Skolasinski1, M. Timm2, C. Meyer2, S. Zeeshan2, A. Naqwi3, A. Panoskaltsis-Mortari4; 1Pulmonary, Allergy, Critical Care, and Sleep, University of Minnesota, Minneapolis, MN, United States, 2University of Minnesota, Minneapolis, MN, United States, 3Abbe Vision, Inc, Minneapolis, MN, United States, 4Univ of Minnesota, Minneapolis, MN, United States.
Purpose: Our goal is to develop a device capable of delivering living cells with high viability into pulmonary airways both ex-vivo and in-vivo.Background: Substantial research is being directed toward developing cell therapies for a wide variety of applications in pulmonary diseases. One example is the use of patient-specific, induced pluripotent stem cell (iPSC)-derived cells to repopulate decellularized lung scaffolds. This could generate immunologically identical transplantable organs by revitalizing unsuitable donor lungs or “humanizing” animal lungs with the potential to eliminate the organ shortage while simultaneously eliminating rejection and the need for rejection medications. However, due to the collapsibility of pulmonary lumina, pulmonary recellularization cannot be accomplished by filling the organ with a cell suspension and rotating it as is done in many other organs. Additionally, pulmonary cells require exposure to an air liquid interface. Therefore, we developed a spray device capable of nondestructively aerosolizing intact cells, and that is sufficiently long and narrow to pass several generations into the bronchial tree. Methods: Multiple prototype sprayers were developed with variations to the spray generation tip and assessed for viability of sprayed cells. Spray velocity, fluid flow rate, and droplet size were measured using phase Doppler interferometry. An illuminated angulation sleeve was designed to allow the sprayer to be navigated through the bronchial tree and visualized through decellularized lung tissue. Pulmonary cells were sprayed through the sprayer into wells of growth media. Cell viability was assessed by trypan blue staining, and growth was assessed by microscopy. Results: The sprayer can deliver pulmonary cells with high cell viability (99 ± 1.2% and 98 ± 3.9% respectively, relative to unsprayed control cells) when assessed by trypan blue staining. The cells appear normal by microscopy immediately after spraying and grow to confluence. Greatest cell survival is seen in devices producing larger droplets at lower velocity and low flow rate. The device could be navigated throughout the bronchial tree to facilitate broad cell delivery throughout the airways, or localized delivery to specific target sites. Conclusions: The microjet sprayer provides a key piece of equipment to translate emerging bioengineering techniques into clinically relevant therapies. The device allows delivery of cells throughout the airways of lung scaffolds and intact lungs. Current studies are aimed at assessing cells sprayed onto intact decellularized bronchial trees. Other potential uses of this device include the in vivo administration of regenerative cells for lung injury and pulmonary diseases amenable to cell therapy.