title: Renal Extracellular Matrix Scaffolds From Discarded Kidneys Maintain Glomerular Morphometry and Vascular Resilience and Retains Critical Growth Factors.
abstract: BACKGROUND
  Extracellular matrix (ECM) scaffolds, obtained through detergent-based decellularization of native kidneys, represent the most promising platform for investigations aiming at manufacturing kidneys for transplant purposes. We previously showed that decellularization of the human kidney yields renal ECM scaffolds (hrECMs) that maintain their basic molecular components, are cytocompatible, stimulate angiogenesis, and show an intact innate vasculature. However, evidence that the decellularization preserves glomerular morphometric characteristics, physiological parameters (pressures and resistances of the vasculature bed), and biological properties of the renal ECM, including retention of important growth factors (GFs), is still missing.
  
  
  METHODS
  To address these issues, we studied the morphometry and resilience of hrECMs' native vasculature with resin casting at electronic microscopy and pulse-wave measurements, respectively. Moreover, we determined the fate of 40 critical GFs post decellularization with a glass chip-based multiplex enzyme-linked immunosorbent assay array and in vitro immunofluorescence.
  
  
  RESULTS
  Our method preserves the 3-dimensional conformation of the native glomerulus. Resin casting and pulse-wave measurements, showed that hrECMs preserves the microvascular morphology and morphometry, and physiological function. Moreover, GFs including vascular endothelial growth factor and its receptors are retained within the matrices.
  
  
  CONCLUSIONS
  Our results indicate that discarded human kidneys are a suitable source of renal scaffolds because they maintain a well-preserved structure and function of the vasculature, as well as GFs that are fundamental to achieve a satisfying recellularization of the scaffold in vivo due to their angiogenic properties.
authors.affiliation: 1 Wake Forest School of Medicine, Winston Salem, NC. 2 General Surgery, Fondazione IRCCS Policlinico San Matteo Pavia and University of Pavia, Pavia, Italy. 3 GOFARR Laboratory, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA. 4 Department of Urology, University of Southern California, Los Angeles, CA. 5 Departments of Biomedical and Mechanical Engineering, Virginia Tech, Blacksburg, VA. 6 Smart Perfusion LLC, Denver, NC.
authors.forename: Andrea
authors.initials: A
authors.lastname: Peloso
authors.forename: Astgik
authors.initials: A
authors.lastname: Petrosyan
authors.forename: Stefano
authors.initials: S
authors.lastname: Da Sacco
authors.forename: Christopher
authors.initials: C
authors.lastname: Booth
authors.forename: Joao Paulo
authors.initials: JP
authors.lastname: Zambon
authors.forename: Timothy
authors.initials: T
authors.lastname: OʼBrien
authors.forename: Charles
authors.initials: C
authors.lastname: Aardema
authors.forename: John
authors.initials: J
authors.lastname: Robertson
authors.forename: Roger E
authors.initials: RE
authors.lastname: De Filippo
authors.forename: Shay
authors.initials: S
authors.lastname: Soker
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Stratta
authors.forename: Laura
authors.initials: L
authors.lastname: Perin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Orlando
mesh_terms: D016319:Corrosion Casting; D005109:Extracellular Matrix / Q000737:chemistry / Q000648:ultrastructure; D006439:Hemodynamics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D055806:Microvessels / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D010477:Perfusion; D040081:Protein Array Analysis; D063177:Pulse Wave Analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor