Therapeutic effects of umbilical cord blood derived mesenchymal stem cell-Conditioned medium on pulmonary arterial hypertension in rats

Jae Chul Lee, Choong Ik Cha, Dong Sik Kim, Soo Young Choe

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

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

    Original languageEnglish
    Pages (from-to)472-480
    Number of pages9
    JournalJournal of Pathology and Translational Medicine
    Volume49
    Issue number6
    DOIs
    Publication statusPublished - 2015

    Keywords

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

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine
    • Histology

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