Therapeutic potential of adipose stem cell-derived conditioned medium against pulmonary hypertension and lung fibrosis

Authors

Anandharajan Rathinasabapathy, Pharmacodynamics, University of Florida, Gainesville, FL, USA.
Erin Bruce, Pharmacodynamics, University of Florida, Gainesville, FL, USA.
Andrew Espejo, Pharmacodynamics, University of Florida, Gainesville, FL, USA.
Alana Horowitz, Pharmacodynamics, University of Florida, Gainesville, FL, USA.
Dhivya R. Sudhan, Radiation Oncology, University of Florida, Gainesville, FL, USA.
Anand Nair, Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA.
Dominic Guzzo, Pharmacodynamics, University of Florida, Gainesville, FL, USA.
Joseph Francis, Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA.
Mohan K. Raizada, Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.
Vinayak Shenoy, Pharmacodynamics, University of Florida, Gainesville, FL, USA. shenoyvi@cop.ufl.edu.
Michael J. Katovich, Pharmacodynamics, University of Florida, Gainesville, FL, USA. katovich@cop.ufl.edu.

Document Type

Article

Publication Date

10-1-2016

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.

Publication Source (Journal or Book title)

British journal of pharmacology

First Page

2859

Last Page

79

Recommended Citation

Rathinasabapathy, A., Bruce, E., Espejo, A., Horowitz, A., Sudhan, D. R., Nair, A., Guzzo, D., Francis, J., Raizada, M. K., Shenoy, V., & Katovich, M. J. (2016). Therapeutic potential of adipose stem cell-derived conditioned medium against pulmonary hypertension and lung fibrosis. British journal of pharmacology, 173 (19), 2859-79. https://doi.org/10.1111/bph.13562