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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 total NF-AT staining in the lungs of htMSC i.n and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized, lungs obtained and sections were stained with anti-NF-AT. In A) representative graphs and B) photomicrographs of immunohistochemistry stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.
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pone.0136942.g007: Reduced total NF-AT staining in the lungs of htMSC i.n and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized, lungs obtained and sections were stained with anti-NF-AT. In A) representative graphs and B) photomicrographs of immunohistochemistry stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.

Mentions: Another transcription factor also important for the activation of the immune cells is the NF-AT, which is mostly expressed on T cells, both CD4+, CD8+ and NK cells, and also in the lung tissue, as shown by the literature [40]. NF-AT is the main transcription factor involved in the synthesis of IL-2 and its active form is the non-phosphorilated state, as reviewed [41]. It was very surprising to notice that LLLT by itself was already able to significantly reduce NF-AT activation (Fig 7A). This reduction was no different from that observed when LLL was associated with htMSCs i.n. (Fig 7A).


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 total NF-AT staining in the lungs of htMSC i.n and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized, lungs obtained and sections were stained with anti-NF-AT. In A) representative graphs and B) photomicrographs of immunohistochemistry 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.g007: Reduced total NF-AT staining in the lungs of htMSC i.n and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized, lungs obtained and sections were stained with anti-NF-AT. In A) representative graphs and B) photomicrographs of immunohistochemistry stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.
Mentions: Another transcription factor also important for the activation of the immune cells is the NF-AT, which is mostly expressed on T cells, both CD4+, CD8+ and NK cells, and also in the lung tissue, as shown by the literature [40]. NF-AT is the main transcription factor involved in the synthesis of IL-2 and its active form is the non-phosphorilated state, as reviewed [41]. It was very surprising to notice that LLLT by itself was already able to significantly reduce NF-AT activation (Fig 7A). This reduction was no different from that observed when LLL was associated with htMSCs i.n. (Fig 7A).

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