title: Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats.
abstract: BACKGROUND
  Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may have multiple therapeutic applications for cell based therapy including the treatment of pulmonary artery hypertension (PAH). As low survival rates and potential tumorigenicity of implanted cells could undermine the mesenchymal stem cell (MSC) cell-based therapy, we chose to investigate the use of conditioned medium (CM) from a culture of MSC cells as a feasible alternative.
  
  
  METHODS
  CM was prepared by culturing hUCB-MSCs in three-dimensional spheroids. In a rat model of PAH induced by monocrotaline, we infused CM or the control unconditioned culture media via the tail-vein of 6-week-old Sprague-Dawley rats.
  
  
  RESULTS
  Compared with the control unconditioned media, CM infusion reduced the ventricular pressure, the right ventricle/(left ventricle+interventricular septum) ratio, and maintained respiratory function in the treated animals. Also, the number of interleukin 1α (IL-1α), chemokine (C-C motif) ligand 5 (CCL5), and tissue inhibitor of metalloproteinase 1 (TIMP-1)-positive cells increased in lung samples and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL)-positive cells decreased significantly in the CM treated animals.
  
  
  CONCLUSIONS
  From our in vivo data in the rat model, the observed decreases in the TUNEL staining suggest a potential therapeutic benefit of the CM in ameliorating PAH-mediated lung tissue damage. Increased IL-1α, CCL5, and TIMP-1 levels may play important roles in this regard.
authors.affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, Korea.|Department of Surgery, Brain Korea 21 PLUS Project for Medical Sciences and HBP Surgery and Liver Transplantation, Korea University College of Medicine, Seoul, Korea.|Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Choong Ik
authors.initials: CI
authors.lastname: Cha
authors.affiliation: Department of Surgery, Brain Korea 21 PLUS Project for Medical Sciences and HBP Surgery and Liver Transplantation, Korea University College of Medicine, Seoul, Korea.
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choe
keywords: Apoptosis; Culture media, conditioned; Gene expression; Mesenchymal stromal cells; Pulmonary artery hypertension