Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury

Araújo, Indianara Maria; Abreu, Soraia C.; Maron‐Gutierrez, Tatiana; Cruz, Fernanda Ferreira; Fujisaki, Livia; Carreira, Humberto; Ornellas, Felipe M.; Ornellas, Débora S.; Vieira‐de‐Abreu, Adriana; Castro‐Faria‐Neto, Hugo C.; Ab’Saber, Alexandre Muxfeldt; Teodoro, Walcy Rosolia; Diaz, Bruno L.; Da-Costa, C.P.; Capelozzi, Vera Luíza; Pelosi, Paolo; Morales, Marcelo M.; Rocco, Patrícia Rieken Macêdo

doi:10.1097/ccm.0b013e3181e796d2

Cited by 58 publications

(71 citation statements)

References 38 publications

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“…7A–B) compared with animals in the control group. On the other hand, the decrease in tubular cell apoptosis, also found here in the IR-C group, corroborates the cytoprotective effect of cell therapy; diminution of the apoptotic levels could have reestablished equilibrium in the kinetics of the tubular compartment This improvement induced by BMMCs has been already been shown in several acute and chronic models of disease after diverse kinds of cell therapy [13-15, 71] and seems to be due to the production of pro-survival growth factors [72-74]. …”

Section: Discussionsupporting

confidence: 58%

Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

Ornellas¹,

Ornellas²,

Martini³

et al. 2017

Cell Physiol Biochem

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Background/Aims: We investigated the regenerative capacity of intravenous administration of bone marrow–derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. Methods: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by ^99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. Results: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. Conclusion: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.

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Section: Discussionsupporting

confidence: 58%

Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

Ornellas¹,

Ornellas²,

Martini³

et al. 2017

Cell Physiol Biochem

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“…Irrespective of the route of delivery, MSCs may reduce lung injury and promote repair by interacting with injured resident alveolar and reparative properties [5,26,27]. In our acute study, we observed increased expression of IL-1RA mRNA in lung tissue when over-ventilated animals were pre-treated with MSCs, irrespective of the administration route, while no major changes in the mRNA expression of KGF or HGF were detected among all the groups after 3 h of injurious ventilation.…”

Section: Discussionmentioning

confidence: 49%

“…Since several studies have shown that pulmonary engraftment of MSCs in the lungs does not occur very easily, the ability of MSCs to reduce lung injury in different ALI models is currently attributed to a paracrine effect [26,27]. Irrespective of the route of delivery, MSCs may reduce lung injury and promote repair by interacting with injured resident alveolar and reparative properties [5,26,27].…”

Section: Discussionmentioning

confidence: 99%

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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“…Transplantation of bone marrow-derived MSCs or EPCs has been reported to reduce mortality and ALI induced by endotoxin or sepsis in rodent models [Yamada et al, 2004;Gupta et al, 2007;Mei et al, 2007;Xu et al, 2007bXu et al, , 2008Nemeth et al, 2009;Araujo et al, 2010;Mao et al, 2010;Mei et al, 2010;Danchuk et al, 2011]. Although it has been shown that transplantation of bone marrow-derived mononuclear cells (BM-MNCs) in a model of LPSinduced ALI led to a repair of alveolar endothelium and epithelium and improvement in lung mechanics [Prota et al, 2010], studies focused on MSCs show that the mechanism of action of bone marrow-derived stem cells is predominantly paracrine [Lee et al, 2011a], with the release of molecules that have not only immunomodulatory effects but also act as growth factors, factors regulating endothelial and epithelial permeability and antimicrobial peptides that can potentially treat the major abnormalities underlying ALI, including impaired airway fluid clearance, altered lung endothelial permeability, dysregulated inflammation and infection ( fig.…”

Section: Acute Lung Injurymentioning

confidence: 99%

Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases

Conese

Carbone

Castellani

et al. 2013

Cells Tissues Organs

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Stem cell-based treatment may represent a hope for the treatment of acute lung injury and pulmonary fibrosis, and other chronic lung diseases, such as cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). It is well established in preclinical models that bone marrow-derived stem and progenitor cells exert beneficial effects on inflammation, immune responses and repairing of damage in virtually all lung-borne diseases. While it was initially thought that the positive outcome was due to a direct engraftment of these cells into the lung as endothelial and epithelial cells, paracrine factors are now considered the main mechanism through which stem and progenitor cells exert their therapeutic effect. This knowledge has led to the clinical use of marrow cells in pulmonary hypertension with endothelial progenitor cells (EPCs) and in COPD with mesenchymal stromal (stem) cells (MSCs). Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells, MSCs, EPCs and fibrocytes, encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine and applied to lung disorders.

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Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury

Cited by 58 publications

References 38 publications

Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

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

Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases

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