Mechanisms of cellular therapy in respiratory diseases

Abreu, Soraia C.; Antunes, Mariana A.; Pelosi, Paolo; Morales, Marcelo M.; Rocco, Patrícia Rieken Macêdo

doi:10.1007/s00134-011-2268-3

Cited by 61 publications

(44 citation statements)

References 73 publications

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“…Whereas some studies on the protective effects of adult stem cells in lung injury have been carried out using bone marrowderived mononuclear cells, including both mesenchymal and hematopoietic stem cells [4][5][6], in this work we focused on MSCs exclusively. We used well-characterised MSCs [15] and applied a number of cells in keeping with the different doses reported in the literature when these stem cells were applied, either intravenously or intratracheally, in rats and mice [10,24].…”

Section: Discussionmentioning

confidence: 99%

“…One control group was kept under spontaneous breathing for the entire duration of the experiment, while the other three groups of rats were tracheostomised and intubated (cannula 16GA BD Adsyte Pro, Becton Dickinson; Madrid, Spain). Subsequently, one group was kept under spontaneous breathing and the animals from another two groups were subjected to the following interventions: 1) injection of 5610 6 MSCs diluted in 0.3 mL of sterile Dulbecco's phosphate-buffered saline (DPBS) through the penile vein; 2) intratracheal instillation of 0.3 mL of DPBS containing 5610 6 MSCs through the intubation cannula. During the intratracheal instillation experiments, the rats were maintained in a head-up tilted position to prevent MSC spillage.…”

Section: Mscsmentioning

confidence: 99%

“…A cell therapy approach recently proposed as a potential treatment for ALI/ARDS is based on the use of bone-marrow derived mesenchymal stem cells (MSCs) [5][6][7]. The rationale for applying adult stem cells of this type derives from their immunosuppressive and anti-inflammatory properties and their freedom from host rejection, allowing them to be used in allotransplantation [8,9].…”

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Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury

et al. 2012

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Bone marrow-derived mesenchymal stem cells (MSCs) reduce acute lung injury in animals challenged by bleomycin or bacterial lipopolysaccaride. It is not known, however, whether MSCs protect from ventilator-induced lung injury (VILI).This study investigated whether MSCs have a potential role in preventing or modulating VILI in healthy rats subjected to high-volume ventilation.24 Sprague-Dawley rats (250-300 g) were subjected to high-volume mechanical ventilation (25 mL?kg -1 ). MSCs (5610 6 ) were intravenously or intratracheally administered (n58 each) 30 min before starting over-ventilation and eight rats were MSC-untreated. Spontaneously breathing anesthetised rats (n58) served as controls. After 3 h of over-ventilation or control the animals were sacrificed and lung tissue and bronchoalveolar lavage fluid (BALF) were sampled for further analysis.When compared with controls, MSC-untreated over-ventilated rats exhibited typical VILI features. Lung oedema, histological lung injury index, concentrations of total protein, interleukin1b, macrophage inflammatory protein-2 and number of neutrophils in BALF and vascular cell adhesion protein-1 in lung tissue significantly increased in over-ventilated rats. All these indices of VILI moved significantly towards normalisation in the rats treated with MSCs, whether intravenously or intratracheally. Both local and systemic pre-treatment with MSCs reduced VILI in a rat model.

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Section: Discussionmentioning

confidence: 99%

Section: Mscsmentioning

confidence: 99%

mentioning

confidence: 99%

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Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury

et al. 2012

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“…Several studies have reported on the beneficial effects of bone marrow cell therapy in different models of lung injury [5,6,7,8,9,10]. In experimental models of lung fibrosis, bone marrow-derived cells (BMDCs) were able to repair damaged tissue by modulating the inflammatory process and replacing damaged cells [3,5,6,7].…”

Section: Introductionmentioning

confidence: 99%

Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

Lopes‐Pacheco

Xisto

Ornellas

et al. 2013

Cell Physiol Biochem

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Background/Aims: Bone marrow-derived cells (BMDCs) reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression. Methods: One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT]) and control (C) groups (saline, IT). C and SIL groups were further randomized to receive BMDCs (2×10⁶ cells) or saline IT 15 and 30 days after the start of the protocol. Results: By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype), apoptotic cells, the level of transforming growth factor (TGF)-β‚ and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL)-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA. Conclusion: repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.

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“…9,10 Moreover, the ability of MSCs to home to injured tissues 16 may obviate the need for local delivery strategies, and may result in localized therapeutic benefit after systemic delivery. 17 We wished to determine the efficacy of intratracheal MSC therapy, gain insights into the mechanisms underlying these effects, and compare the efficacy of this approach with that of intravenous MSC therapy. 11 We hypothesized that intratracheal delivery of MSCs would (1) enhance functional recovery and lung repair after VILI; (2) that these effects would be mediated via a paracrine mechanism; and (3) that the efficacy of intratracheal delivery would be similar to intravenous MSC therapy.…”

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Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury

et al. 2013

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Background: Mesenchymal stromal cells (MSCs) have been demonstrated to attenuate acute lung injury when delivered by intravenous or intratracheal routes. The authors aimed to determine the efficacy of and mechanism of action of intratracheal MSC therapy and to compare their efficacy in enhancing lung repair after ventilation-induced lung injury with intravenous MSC therapy. Methods: After induction of anesthesia, rats were orotracheally intubated and subjected to ventilation-induced lung injury (respiratory rate 18 min −1 , P insp 35 cm H 2 O,) to produce severe lung injury. After recovery, animals were randomized to receive: (1) no therapy, n = 4; (2) intratracheal vehicle (phosphate-buffered saline, 300 µl, n = 8); (3) intratracheal fibroblasts (4 × 10 6 cells, n = 8); (4) intratracheal MSCs (4 × 10 6 cells, n = 8); (5) intratracheal conditioned medium (300 µl, n = 8); or (6) intravenous MSCs (4 × 10 6 cells, n = 4). The extent of recovery after acute lung injury and the inflammatory response was assessed after 48 h. Results: Intratracheal MSC therapy enhanced repair after ventilation-induced lung injury, improving arterial oxygenation (mean ± SD, 146 ± 3.9 vs. 110.8 ± 21.5 mmHg), restoring lung compliance (1.04 ± 0.11 vs. 0.83 ± 0.06 ml·cm H 2 O −1 ), reducing total lung water, and decreasing lung inflammation and histologic injury compared with control. Intratracheal MSC therapy attenuated alveolar tumor necrosis factor-α (130 ± 43 vs. 488 ± 211 pg·ml −1) and interleukin-6 concentrations (138 ± 18 vs. 260 ± 82 pg·ml −1 ). The efficacy of intratracheal MSCs was comparable with

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Mechanisms of cellular therapy in respiratory diseases

Abstract: A better understanding of the mechanisms that control cell division and differentiation, as well as of their paracrine effects, is required to enable the optimal use of bone marrow-derived stem cell therapy to treat human respiratory diseases.

Cited by 61 publications

References 73 publications

Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury

Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury

Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury

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