Anandharajan Rathinasabapathy1,2, Erin Bruce1, Andrew Espejo1, Alana Horowitz1, Dhivya R Sudhan3, Anand Nair4,5, Dominic Guzzo1, Joseph Francis4, Mohan K Raizada6, Vinayak Shenoy7,8, Michael J Katovich9. 1. Pharmacodynamics, University of Florida, Gainesville, FL, USA. 2. Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 3. Radiation Oncology, University of Florida, Gainesville, FL, USA. 4. Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA. 5. Pharmacology, University of Iowa, Iowa City, IA, USA. 6. Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA. 7. Pharmacodynamics, University of Florida, Gainesville, FL, USA. shenoyvi@cop.ufl.edu. 8. Pharmaceutical and Biomedical Sciences, California Health Sciences University, Clovis, CA, USA. shenoyvi@cop.ufl.edu. 9. Pharmacodynamics, University of Florida, Gainesville, FL, USA. katovich@cop.ufl.edu.
Abstract
BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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.
BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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.
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