title: Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.
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.
authors: Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.
authors: Jean Pierre Schatzmann
authors: JP
authors: Peron
authors: Laboratory of Pulmonary and Exercise Immunology-LABPEI, Nove de Julho University (UNINOVE), São Paulo, SP, Brazil.
authors: Auriléia Aparecida
authors: AA
authors: de Brito
authors: Division of Human Genome Research Center, Biosciences Institute, University of São Paulo, São Paulo, SP, Brazil.
authors: Mayra
authors: M
authors: Pelatti
authors: Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.
authors: Wesley Nogueira
authors: WN
authors: Brandão
authors: Laboratory of Pulmonary and Exercise Immunology-LABPEI, Nove de Julho University (UNINOVE), São Paulo, SP, Brazil.
authors: Luana Beatriz
authors: LB
authors: Vitoretti
authors: Laboratory of Pulmonary and Exercise Immunology-LABPEI, Nove de Julho University (UNINOVE), São Paulo, SP, Brazil.
authors: Flávia Regina
authors: FR
authors: Greiffo
authors: Laboratory of Pulmonary and Exercise Immunology-LABPEI, Nove de Julho University (UNINOVE), São Paulo, SP, Brazil.
authors: Elaine Cristina
authors: EC
authors: da Silveira
authors: Division of Human Genome Research Center, Biosciences Institute, University of São Paulo, São Paulo, SP, Brazil.
authors: Manuel Carneiro
authors: MC
authors: Oliveira-Junior
authors: CEERH-Specialized Center for Human Reproduction, Division of Reproductive Medicine, São Paulo, SP, Brazil.
authors: Mariangela
authors: M
authors: Maluf
authors: Division of Reproductive Medicine-Célula Mater, São Paulo, SP, Brazil.
authors: Lucila
authors: L
authors: Evangelista
authors: Division of Reproductive Medicine-Célula Mater, São Paulo, SP, Brazil.
authors: Silvio
authors: S
authors: Halpern
authors: Division of Reproductive Medicine-Célula Mater, São Paulo, SP, Brazil.
authors: Marcelo Gil
authors: MG
authors: Nisenbaum
authors: CEERH-Specialized Center for Human Reproduction, Division of Reproductive Medicine, São Paulo, SP, Brazil.
authors: Paulo
authors: P
authors: Perin
authors: Division of Reproductive Medicine-Célula Mater, São Paulo, SP, Brazil.
authors: Carlos Eduardo
authors: CE
authors: Czeresnia
authors: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors: Niels Olsen Saraiva
authors: NO
authors: Câmara
authors: Department of Science and Technology, Federal University of São Paulo, São José dos Campos, SP, Brazil.
authors: Flávio
authors: F
authors: Aimbire
authors: Division of Human Genome Research Center, Biosciences Institute, University of São Paulo, São Paulo, SP, Brazil.
authors: Rodolfo de Paula
authors: RP
authors: Vieira
authors: Laboratory of Pulmonary and Exercise Immunology-LABPEI, Nove de Julho University (UNINOVE), São Paulo, SP, Brazil.
authors: Mayana
authors: M
authors: Zatz
authors: Division of Human Genome Research Center, Biosciences Institute, University of São Paulo, São Paulo, SP, Brazil.
authors: Ana Paula Ligeiro
authors: AP
authors: de Oliveira
mesh_terms: D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D028022:Low-Level Light Therapy / Q000379:methods; D008168:Lung / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced* / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha