title: Assessment of Proliferation and Cytotoxicity in a Biomimetic Three-Dimensional Model of Lung Cancer.
abstract: BACKGROUND
  Decellularized whole-organ scaffolds show great potential in cancer research. They have been used in the biomimetic three-dimensional (3D) culture of non-small cell lung cancer cells, allowing the study of unique aspects of lung cancer biology. However, there are no reproducible assays capable of directly monitoring processes involved in cancer progression within such scaffolds.
  
  
  METHODS
  The human adenocarcinoma cell lines H358, PC9, and SW1573 were subjected to biomimetic 3D culture within decellularized lung scaffolds. A resazurin-based reagent was perfused through the scaffold to determine cell viability over the culture period and in response to treatment with cisplatin or erlotinib.
  
  
  RESULTS
  The resazurin reduction perfusion assay detected a progressive increase in the reduction of resazurin over time for all cell lines cultured within decellularized lung scaffolds, translating into incremental cell populations. Also, it detected a positive cytotoxic effect in H358- and PC9-seeded scaffolds after treatment with cisplatin, and in PC9-seeded scaffolds after treatment with erlotinib. Moreover, it identified relative resistance to erlotinib in H358- and SW1573-seeded scaffolds. Results from this assay correlated with histopathology, expression of caspase 3, and activity of epidermal growth factor receptor signaling.
  
  
  CONCLUSIONS
  The methods described here for the monitoring of lung cancer cell viability under biomimetic 3D culture conditions within decellularized lung scaffolds permit the study of cancer cell proliferation, the evaluation of responses to therapeutic interventions, and the determination of relative chemo-sensitivities.
authors.affiliation: Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Tapias
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gilpin
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Xi
authors.initials: X
authors.lastname: Ren
authors.affiliation: Division of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Lan
authors.initials: L
authors.lastname: Wei
authors.affiliation: Division of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Fuchs
authors.affiliation: Division of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Tanabe
authors.affiliation: Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Lanuti
authors.affiliation: Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Harvard Stem Cell Institute, Boston, Massachusetts. Electronic address: hott@mgh.harvard.edu.
authors.forename: Harald C
authors.initials: HC
authors.lastname: Ott
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D032701:Biomimetics; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000627:therapeutic use*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin