Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats.
- Author:
Jae Chul LEE
1
;
Choong Ik CHA
;
Dong Sik KIM
;
Soo Young CHOE
Author Information
- Publication Type:Retracted Publication ; Original Article
- Keywords: Apoptosis; Culture media, conditioned; Gene expression; Mesenchymal stromal cells; Pulmonary artery hypertension
- MeSH: Animals; Apoptosis; Culture Media; Culture Media, Conditioned; Deoxyuridine; Fetal Blood*; Gene Expression; Humans; Hypertension*; In Situ Nick-End Labeling; Interleukin-1alpha; Lung; Mesenchymal Stromal Cells; Models, Animal; Monocrotaline; Pulmonary Artery; Rats*; Rats, Sprague-Dawley; Survival Rate; Tissue Inhibitor of Metalloproteinase-1; Umbilical Cord*; Ventricular Pressure
- From:Journal of Pathology and Translational Medicine 2015;49(6):472-480
- CountryRepublic of Korea
- Language:English
- 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.
