title: Therapeutic potential of adipose stem cell-derived conditioned medium against pulmonary hypertension and lung fibrosis.
abstract: Pulmonary hypertension (PH) and pulmonary fibrosis (PF) are life threatening cardiopulmonary diseases. Existing pharmacological interventions have failed to improve clinical outcomes or reduce disease-associated mortality. Emerging evidence suggests that stem cells offer an effective treatment approach against various pathological conditions. It has been proposed that their beneficial actions may be mediated via secretion of paracrine factors. Herein, we evaluated the therapeutic potential of conditioned media (CM) from adipose stem cells (ASCs) against experimental models of PH and PF.
  
  
  
  Monocrotaline (MCT) or bleomycin (Bleo) was injected into male Sprague-Dawley rats to induce PH or PF respectively. A subset of MCT and Bleo animals were treated with ASCs or CM. Echocardiographic and haemodynamic measurements were performed at the end of the study. Lung and heart tissues were harvested for RNA, protein and histological measurements.
  
  
  
  CM treatment attenuated MCT-induced PH by improving pulmonary blood flow and inhibiting cardiac remodelling. Further, histological studies revealed that right ventricular fibrosis, pulmonary vessel wall thickness and pericyte distribution were significantly decreased by CM administration. Likewise, CM therapy arrested the progression of PF in the Bleo model by reducing collagen deposition. Elevated expression of markers associated with tissue remodelling and inflammation were significantly reduced in both PF and PH lungs. Similar results were obtained with ASCs administration.
  
  
  
  Our study indicates that CM treatment is as effective as ASCs in treating PH and PF. These beneficial effects of CM may provide an innovative approach to treat cardiopulmonary disorders.
authors.affiliation: Pharmacodynamics, University of Florida, Gainesville, FL, USA.|Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Anandharajan
authors.initials: A
authors.lastname: Rathinasabapathy
authors.affiliation: Pharmacodynamics, University of Florida, Gainesville, FL, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Bruce
authors.affiliation: Pharmacodynamics, University of Florida, Gainesville, FL, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Espejo
authors.affiliation: Pharmacodynamics, University of Florida, Gainesville, FL, USA.
authors.forename: Alana
authors.initials: A
authors.lastname: Horowitz
authors.affiliation: Radiation Oncology, University of Florida, Gainesville, FL, USA.
authors.forename: Dhivya R
authors.initials: DR
authors.lastname: Sudhan
authors.affiliation: Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA.|Pharmacology, University of Iowa, Iowa City, IA, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Nair
authors.affiliation: Pharmacodynamics, University of Florida, Gainesville, FL, USA.
authors.forename: Dominic
authors.initials: D
authors.lastname: Guzzo
authors.affiliation: Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
authors.affiliation: Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
authors.affiliation: Pharmacodynamics, University of Florida, Gainesville, FL, USA. shenoyvi@cop.ufl.edu.|Pharmaceutical and Biomedical Sciences, California Health Sciences University, Clovis, CA, USA. shenoyvi@cop.ufl.edu.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Shenoy
authors.affiliation: Pharmacodynamics, University of Florida, Gainesville, FL, USA. katovich@cop.ufl.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Katovich
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D001761:Bleomycin; D016686:Monocrotaline