Abstract
IntroductionHuman umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may have multiple therapeutic applications cell based therapy with one being for treatment of pulmonary artery hypertension. As low survival rates and potential tumorigenicity of implanted cells could undermine the mesenchymal stem cell-based therapy, we chose to investigate the use of conditioned medium (CM) from a culture of MSC cells. Material and methodsCM 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 tail-vein of 6-week-old Sprague-Dawley rats. ResultsCompared 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 IL-1α, CCL5 and TIMP-1-positive cells increased in lung samples and the number of TUNEL-positive cells decreased significantly in the CM treated animals. DiscussionFrom our in vivo data in the rat model, the observed decreases in the TUNEL staining point to 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.
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