TY - JOUR
T1 - Therapeutic effects of umbilical cord blood derived mesenchymal stem cell-conditioned medium on pulmonary arterial hypertension in rats
AU - Lee, Jae Chul
AU - Cha, Choong Ik
AU - Kim, Dongsik
AU - Choe, Soo Young
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Introduction Human 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 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 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 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. Discussion From 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.
AB - Introduction Human 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 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 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 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. Discussion From 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.
KW - Apoptosis
KW - Conditioned medium
KW - Gene expression
KW - Mesenchymal stem cells
KW - Pulmonary artery hypertension
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U2 - 10.1016/j.jasi.2016.07.005
DO - 10.1016/j.jasi.2016.07.005
M3 - Article
AN - SCOPUS:84994533145
VL - 65
SP - 15
EP - 19
JO - Journal of the Anatomical Society of India
JF - Journal of the Anatomical Society of India
SN - 0003-2778
IS - 1
ER -