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

Lee JC, Cha CI, Kim DS, Choe SY - J Pathol Transl Med (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, 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 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.

No MeSH data available.


Related in: MedlinePlus

Changes of IL-1α, CCL5, and TIMP-1 protein expression levels after hUCB-MSCs-CM injection in PAH rats. (A) These are pictures of protein expression levels of IL-1α, CCL5, and TIMP-1 in the lung tissues. (B) The protein expressions levels of IL-1α, CCL5, and TIMP-1 at 28 days are significantly increased in the CM group compared to the C and M groups. The protein expressions of CCL are increased in the M group compared to the C group. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.
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f3-jptm-2015-09-11: Changes of IL-1α, CCL5, and TIMP-1 protein expression levels after hUCB-MSCs-CM injection in PAH rats. (A) These are pictures of protein expression levels of IL-1α, CCL5, and TIMP-1 in the lung tissues. (B) The protein expressions levels of IL-1α, CCL5, and TIMP-1 at 28 days are significantly increased in the CM group compared to the C and M groups. The protein expressions of CCL are increased in the M group compared to the C group. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.

Mentions: The protein expressions of CCL5 at 28 days were significantly increased in the M group compared to the C group. The protein expressions of TIMP-1, IL-1α, and CCL5 at 28 days were significantly increased in the CM group compared to the M group (Fig. 3). The protein expressions of caspase-3 and Bcl-2 were significantly increased in the M group compared to the C group at 28 days. The protein expressions of caspase-3 and Bcl-2 were significantly decreased in the CM group compared to the M group at 28 days (Fig. 4).


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

Lee JC, Cha CI, Kim DS, Choe SY - J Pathol Transl Med (2015)

Changes of IL-1α, CCL5, and TIMP-1 protein expression levels after hUCB-MSCs-CM injection in PAH rats. (A) These are pictures of protein expression levels of IL-1α, CCL5, and TIMP-1 in the lung tissues. (B) The protein expressions levels of IL-1α, CCL5, and TIMP-1 at 28 days are significantly increased in the CM group compared to the C and M groups. The protein expressions of CCL are increased in the M group compared to the C group. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696528&req=5

f3-jptm-2015-09-11: Changes of IL-1α, CCL5, and TIMP-1 protein expression levels after hUCB-MSCs-CM injection in PAH rats. (A) These are pictures of protein expression levels of IL-1α, CCL5, and TIMP-1 in the lung tissues. (B) The protein expressions levels of IL-1α, CCL5, and TIMP-1 at 28 days are significantly increased in the CM group compared to the C and M groups. The protein expressions of CCL are increased in the M group compared to the C group. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.
Mentions: The protein expressions of CCL5 at 28 days were significantly increased in the M group compared to the C group. The protein expressions of TIMP-1, IL-1α, and CCL5 at 28 days were significantly increased in the CM group compared to the M group (Fig. 3). The protein expressions of caspase-3 and Bcl-2 were significantly increased in the M group compared to the C group at 28 days. The protein expressions of caspase-3 and Bcl-2 were significantly decreased in the CM group compared to the M group at 28 days (Fig. 4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, 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 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.

No MeSH data available.


Related in: MedlinePlus