J Pathol Transl Med.  2015 Nov;49(6):472-480. 10.4132/jptm.2015.09.11.

Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats

Affiliations
  • 1Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, Korea. leejc@chungbuk.ac.kr
  • 2Department of Surgery, Brain Korea 21 PLUS Project for Medical Sciences and HBP Surgery and Liver Transplantation, Korea University College of Medicine, Seoul, Korea. beas100@korea.ac.kr
  • 3Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.

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 1alpha (IL-1alpha), 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-1alpha, CCL5, and TIMP-1 levels may play important roles in this regard.

Keyword

Apoptosis; Culture media, conditioned; Gene expression; Mesenchymal stromal cells; Pulmonary artery hypertension
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