title: Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists.
abstract: Human precision-cut lung slices (hPCLSs) provide a unique ex vivo model for translational research. However, the limited and unpredictable availability of human lung tissue greatly impedes their use. Here, we demonstrate that cryopreservation of hPCLSs facilitates banking of live human lung tissue for routine use. Our results show that cryopreservation had little effect on overall cell viability and vital functions of immune cells, including phagocytes and T lymphocytes. In addition, airway contraction and relaxation in response to specific agonists and antagonists, respectively, were unchanged after cryopreservation. At the subcellular level, cryopreserved hPCLSs maintained Ca(2+)-dependent regulatory mechanisms for the control of airway smooth muscle cell contractility. To exemplify the use of cryopreserved hPCLSs in smooth muscle research, we provide evidence that bitter-taste receptor (TAS2R) agonists relax airways by blocking Ca(2+) oscillations in airway smooth muscle cells. In conclusion, the banking of cryopreserved hPCLSs provides a robust bioassay for translational research of lung physiology and disease.
authors.affiliation: 1 Pulmonary, Allergy, Sleep and Critical Care Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: 2 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and.
authors.forename: Nandini
authors.initials: N
authors.lastname: Krishnamoorthy
authors.affiliation: 1 Pulmonary, Allergy, Sleep and Critical Care Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Kruti R
authors.initials: KR
authors.lastname: Patel
authors.affiliation: 2 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosas
authors.affiliation: 3 Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sanderson
authors.affiliation: 1 Pulmonary, Allergy, Sleep and Critical Care Medicine, Boston University School of Medicine, Boston, Massachusetts.|2 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Ai
mesh_terms: D001681:Biological Assay / Q000379:methods*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015925:Cryopreservation; D006801:Humans; D008168:Lung / Q000166:cytology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013649:Taste / Q000187:drug effects*; D014015:Tissue Banks
chemical_list: D001993:Bronchodilator Agents; D043562:Receptors, G-Protein-Coupled
keywords: Ca2+ oscillations; biobank; bitter-taste receptor; cryopreservation; human precision-cut lung slices