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Peron J.P.S.,University of Sao Paulo | De Brito A.A.,Nove de Julho University | Pelatti M.,University of Sao Paulo | Brandao W.N.,University of Sao Paulo | And 11 more authors.
PLoS ONE | Year: 2015

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 cotherapy 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. © 2015 Peron et al.


PubMed | Federal University of São Paulo, Specialized Center for Human Reproduction, University of Sao Paulo and Nove de Julho University
Type: Journal Article | Journal: PloS one | Year: 2015

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-1, IL-6, TNF- 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-B 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.


Jazedje T.,University of Sao Paulo | Bueno D.F.,University of Sao Paulo | Almada B.V.P.,University of Sao Paulo | Caetano H.,University of Sao Paulo | And 9 more authors.
Stem Cell Reviews and Reports | Year: 2012

We have recently reported that human fallopian tubes, which are discarded during surgical procedures of women submitted to sterilization or hysterectomies, are a rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has been previously shown that human mesenchymal stromal cells may be useful in enhancing the speed of bone regeneration. This prompted us to investigate whether htMSCs might be useful for the treatment of osteoporosis or other bone diseases, since they present a pronounced capacity for osteogenic differentiation in vitro. Based on this prior knowledge, our aim was to evaluate, in vivo, the osteogenic capacity of htMSCs to regenerate bone through an already described xenotransplantation model: nonimmunosuppressed (NIS) rats with cranial defects. htMSCs were obtained from five 30-50 years old healthy women and characterized by flow cytometry and for their multipotenciality in vitro capacity (osteogenic, chondrogenic and adipogenic differentiations). Two symmetric full-thickness cranial defects on each parietal region of seven NIS rats were performed. The left side (LS) of six animals was covered with CellCeram (Scaffdex)-a bioabsorbable ceramic composite scaffold that contains 60% hydroxyapatite and 40% β-tricalciumphosphate-only, and the right side (RS) with the CellCeram and htMSCs (10 6 cells/scaffold). The animals were euthanized at 30, 60 and 90 days postoperatively and cranial tissue samples were taken for histological analysis. After 90 days we observed neobone formation in both sides. However, in animals euthanized 30 and 60 days after the procedure, a mature bone was observed only on the side with htMSCs. PCR and immunofluorescence analysis confirmed the presence of human DNA and thus that human cells were not rejected, which further supports the imunomodulatory property of htMSCs. In conclusion, htMSCs can be used successfully to enhance bone regeneration in vivo, opening a new field for future treatments of osteoporosis and bone reconstruction. © 2011 The Author(s).


Perin P.M.,University of Sao Paulo | Perin P.M.,Specialized Center for Human Reproduction | Maluf M.,University of Sao Paulo | Maluf M.,Specialized Center for Human Reproduction | And 4 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2010

Purpose: To assess the potential effects of short-term exposure to particulate air pollution during follicular phase on clinical, laboratory, and pregnancy outcomes of women undergoing IVF/ET. Methods: Retrospective cohort study of 400 first IVF/ET cycles of women exposed to ambient particulate matter during follicular phase. Particulate matter (PM) was categorized into quartiles (Q1: ≤30.48 μg/m3, Q2: 30.49-42.00 μg/m3, Q3: 42.01-56.72 μg/m3, and Q 4: >56.72 μg/m3). Results: Clinical, laboratory, or treatment variables were not affected by follicular phase PM exposure periods. Women exposed to Q4 period during the follicular phase of conception cycles had a higher risk of miscarriage (odds ratio, 5.05; 95% confidence interval: 1.04-25.51) when compared to women exposed to Q1-3 periods. Conclusion: Our results show an association between brief exposure to high levels of ambient PM during the preconceptional period and early pregnancy loss, although no effect of this exposure on clinical, laboratory, and treatment outcomes was observed. © 2010 Springer Science+Business Media, LLC.


Perin P.M.,University of Sao Paulo | Perin P.M.,Specialized Center for Human Reproduction | Maluf M.,University of Sao Paulo | Maluf M.,Specialized Center for Human Reproduction | And 4 more authors.
Fertility and Sterility | Year: 2010

The objective of this retrospective cohort study was to assess the potential effects of preconceptional short-term exposure to particulate air pollution in a real-world situation on pregnancy outcome in infertile women evaluating the possible role of IVF/embryo transfer treatment on this outcome using women who had conceived naturally for the first time during the same time frame as a matched control group. The study provides evidence for an association between brief exposure to high levels of ambient particulate matter (aerodynamic diameter ≤10 μm) during the preconceptional period and early pregnancy loss, regardless of the method of conception, and showed a 2.6-fold increase in risk of miscarriage, suggesting a threshold instead of a monotonic effect of this exposure on reproductive outcome. © 2010 American Society for Reproductive Medicine.

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