title: Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study.
abstract: BACKGROUND
  Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI. The goal of the study was therefore to determine if intratracheal MAPC instillation would decrease lung injury and inflammation in an ex vivo human lung explant model of prolonged cold storage and subsequent reperfusion.
  
  
  METHODS
  Four donor lungs not utilized for transplant underwent 8 h of cold storage (4°C). Following rewarming for approximately 30 min, non-HLA-matched allogeneic MAPCs (1 × 10(7) MAPCs/lung) were bronchoscopically instilled into the left lower lobe (LLL) and vehicle comparably instilled into the right lower lobe (RLL). The lungs were then perfused and mechanically ventilated for 4 h and subsequently assessed for histologic injury and for inflammatory markers in bronchoalveolar lavage fluid (BALF) and lung tissue.
  
  
  RESULTS
  All LLLs consistently demonstrated a significant decrease in histologic and BALF inflammation compared to vehicle-treated RLLs.
  
  
  CONCLUSIONS
  These initial pilot studies suggest that use of non-HLA-matched allogeneic MAPCs during donor lung processing can decrease markers of cold ischemia-induced lung injury.
authors: Cardiac Surgery and Cardiopulmonary Transplantation, DeBakey Heart and Vascular Center, The Houston Methodist, Houston, TX USA ; Harvard Apparatus Regenerative Technology, Inc, Holliston, MA USA.
authors: Saverio
authors: S
authors: La Francesca
authors: Athersys Inc, Cleveland, OH USA.
authors: Anthony E
authors: AE
authors: Ting
authors: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX USA.
authors: Jason
authors: J
authors: Sakamoto
authors: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX USA.
authors: Jessica
authors: J
authors: Rhudy
authors: Department of Medicine, University of Vermont College of Medicine, 226 Health Science Research Facility, Burlington, VT USA.
authors: Nicholas R
authors: NR
authors: Bonenfant
authors: Department of Medicine, University of Vermont College of Medicine, 226 Health Science Research Facility, Burlington, VT USA.
authors: Zachary D
authors: ZD
authors: Borg
authors: Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Fernanda F
authors: FF
authors: Cruz
authors: Department of Medicine, University of Vermont College of Medicine, 226 Health Science Research Facility, Burlington, VT USA.
authors: Meagan
authors: M
authors: Goodwin
authors: Athersys Inc, Cleveland, OH USA.
authors: Nicholas A
authors: NA
authors: Lehman
authors: Athersys Inc, Cleveland, OH USA.
authors: Jennifer M
authors: JM
authors: Taggart
authors: Athersys Inc, Cleveland, OH USA.
authors: Robert
authors: R
authors: Deans
authors: Department of Medicine, University of Vermont College of Medicine, 226 Health Science Research Facility, Burlington, VT USA.
authors: Daniel J
authors: DJ
authors: Weiss
keywords: Cell therapy; Ischemia-reperfusion injury; Lung transplantation; Mesenchymal stromal cell