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Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Peron JP, de Brito AA, Pelatti M, Brandão WN, Vitoretti LB, Greiffo FR, da Silveira EC, Oliveira-Junior MC, Maluf M, Evangelista L, Halpern S, Nisenbaum MG, Perin P, Czeresnia CE, Câmara NO, Aimbire F, Vieira Rde P, Zatz M, de Oliveira AP - PLoS ONE (2015)

Bottom Line: Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease.We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage.These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10.

View Article: PubMed Central - PubMed

Affiliation: Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.

ABSTRACT
Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

No MeSH data available.


Related in: MedlinePlus

Reduced collagen deposition only in the lungs of htMSC i.n and LLL treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and lungs were obtained and sections were stained with Sirus Red for collagen detection. In A) representative graphs and B) photomicrographs of Sirius Red stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.
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pone.0136942.g005: Reduced collagen deposition only in the lungs of htMSC i.n and LLL treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and lungs were obtained and sections were stained with Sirus Red for collagen detection. In A) representative graphs and B) photomicrographs of Sirius Red stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.

Mentions: Aside from mucus secretion, collagen deposition is also considered an important marker for COPD. Therefore, we also evaluated the amount of peribronchial collagen deposition through Sirius Red methodology (Fig 5A and 5B). Very surprisingly, a significant collagen decrease of around 4-fold was observed only when LLLT was associated with htMSCs intranasally. Although there was a trend for the htMSCs (i.p) + LLLT, none of the other groups reached statistical significance (Fig 5B).


Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Peron JP, de Brito AA, Pelatti M, Brandão WN, Vitoretti LB, Greiffo FR, da Silveira EC, Oliveira-Junior MC, Maluf M, Evangelista L, Halpern S, Nisenbaum MG, Perin P, Czeresnia CE, Câmara NO, Aimbire F, Vieira Rde P, Zatz M, de Oliveira AP - PLoS ONE (2015)

Reduced collagen deposition only in the lungs of htMSC i.n and LLL treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and lungs were obtained and sections were stained with Sirus Red for collagen detection. In A) representative graphs and B) photomicrographs of Sirius Red stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554986&req=5

pone.0136942.g005: Reduced collagen deposition only in the lungs of htMSC i.n and LLL treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and lungs were obtained and sections were stained with Sirus Red for collagen detection. In A) representative graphs and B) photomicrographs of Sirius Red stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.
Mentions: Aside from mucus secretion, collagen deposition is also considered an important marker for COPD. Therefore, we also evaluated the amount of peribronchial collagen deposition through Sirius Red methodology (Fig 5A and 5B). Very surprisingly, a significant collagen decrease of around 4-fold was observed only when LLLT was associated with htMSCs intranasally. Although there was a trend for the htMSCs (i.p) + LLLT, none of the other groups reached statistical significance (Fig 5B).

Bottom Line: Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease.We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage.These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10.

View Article: PubMed Central - PubMed

Affiliation: Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.

ABSTRACT
Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

No MeSH data available.


Related in: MedlinePlus