Mesenchymal stem cells transplantation protects against rat pulmonary emphysema

Zhen, Guohua; Li, Hongmei; Gu, Naibing; Zhang, Huilan; Xu, Yongjian; Zhang, Zhenxiang

doi:10.2741/2936

Cited by 111 publications

(82 citation statements)

References 22 publications

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“…Similar protective paracrine effects of BM-derived MSCs have also been demonstrated by several investigators in experimental models of pulmonary emphysema induced by papain [65,66] or intratracheally administered elastase [67]. Based on the above observations, Schweitzer et al [68] suggested that the protective effect of intravenously given human or mouse adult ADSCs in a model of inflammation and injury induced by cigarette smoke exposure was mediated via a paracrine pathway involving growth factors and angiogenic modulators.…”

Section: Stem Cell Therapy In Copdsupporting

confidence: 56%

Stem Cell Treatment for Chronic Lung Diseases

Τzouvelekis

Ntolios

Bouros³

2013

Respiration

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Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few ‘brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn.

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Section: Stem Cell Therapy In Copdsupporting

confidence: 56%

Stem Cell Treatment for Chronic Lung Diseases

Τzouvelekis

Ntolios

Bouros³

2013

Respiration

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“…Innovative therapies are needed. Recent studies have suggested that mesenchymal stem or stromal cells (MSC) may have therapeutic applications in multiple models of lung disease (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Despite initial interest in their multipotent properties, engraftment in the lung does not seem to play a major therapeutic role.…”

mentioning

confidence: 99%

Therapeutic Effects of Human Mesenchymal Stem Cells in Ex Vivo Human Lungs Injured with Live Bacteria

Lee

Krasnodembskaya²,

McKenna

et al. 2013

Am J Respir Crit Care Med

315

349

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Rationale: Mesenchymal stem cells secrete paracrine factors that can regulate lung permeability and decrease inflammation, making it a potentially attractive therapy for acute lung injury. However, concerns exist whether mesenchymal stem cells' immunomodulatory properties may have detrimental effects if targeted toward infectious causes of lung injury.Objectives: Therefore, we tested the effect of mesenchymal stem cells on lung fluid balance, acute inflammation, and bacterial clearance. Methods: We developed an Escherichia coli pneumonia model in our ex vivo perfused human lung to test the therapeutic effects of mesenchymal stem cells on bacterial-induced acute lung injury. Measurements and Main Results: Clinical-grade human mesenchymal stem cells restored alveolar fluid clearance to a normal level, decreased inflammation, and were associated with increased bacterial killing and reduced bacteremia, in part through increased alveolar macrophage phagocytosis and secretion of antimicrobial factors. Keratinocyte growth factor, a soluble factor secreted by mesenchymal stem cells, duplicated most of the antimicrobial effects. In subsequent in vitro studies, we discovered that human monocytes expressed the keratinocyte growth factor receptor, and that keratinocyte growth factor decreased apoptosis of human monocytes through AKT phosphorylation, an effect that increased bacterial clearance. Inhibition of keratinocyte growth factor by a neutralizing antibody reduced the antimicrobial effects of mesenchymal stem cells in the ex vivo perfused human lung and monocytes grown in vitro injured with E. coli bacteria. Conclusions: In E. coli-injured human lungs, mesenchymal stem cells restored alveolar fluid clearance, reduced inflammation, and exerted antimicrobial activity, in part through keratinocyte growth factor secretion.Keywords: acute lung injury; bacterial pneumonia; cell-based therapy; keratinocyte growth factor Despite extensive research into the pathogenesis of acute lung injury (ALI) and the acute respiratory distress syndrome, mortality remains high (1-3). Current treatment is supportive with lung protective ventilation and a fluid conservative strategy (4, 5). Innovative therapies are needed. Recent studies have suggested that mesenchymal stem or stromal cells (MSC) may have therapeutic applications in multiple models of lung disease (6-17). Despite initial interest in their multipotent properties, engraftment in the lung does not seem to play a major therapeutic role. The beneficial effect of MSC derives from their capacity to secrete paracrine factors that modulate immune responses and alter the responses of the endothelium or epithelium and inflammatory cells to injury (17-28). Because of the immunosuppressive properties of MSC, one safety concern is a potential deleterious effect on host defense against bacterial infection. Bacterial pneumonia and sepsis from a nonpulmonary cause are the two most common etiologies of ALI and acute respiratory distress syndrome (2). However, recent studies have provided eviden...

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“…Emphysema, characterized by a loss of alveolar architecture, is a key component present in COPD, and although the pathogenesis of emphysema is still unclear (37), inactivation of vascular endothelial growth factor (VEGF) is crucial in the development of this condition (38). MSCs act in the emphysematous lung through suppression of apoptosis (39,40), downregulation of proinflammatory cytokines TNF-α, IL-1, and IL-6, and upregulation of VEGF and TGFβ-1 (40). In a clinical trial recently conducted by Weiss et al, 62 patients were given doses of either allogeneic MSCs or a placebo, demonstrating the safety of cell therapy for COPD.…”

Section: Mscs In Chronic Lung Diseasesmentioning

confidence: 99%

Mesenchymal stem cells for therapy in lung diseases

Álvarez¹

2014

SOB

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SummaryLung diseases are among the most devastating illnesses because of their prevalence and simultaneous lack of viable treatment. To advance beyond the current options of mechanical ventilation and transplantation, research in recent years has focused on cell therapy, and of the possibilities, mesenchymal stem cells (MSCs) are the most promising. MSCs have immunomodulatory and secretory effects that work to relieve inflammation and prevent fibrosis in response to the injured lung. Numerous small and large animal models have shown the ameliorating effects of MSCs in diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disorder, acute respiratory distress syndrome, obstructive sleep apnea, bronchiolitis obliterans, and asthma. Clinical trials for MSC use in some of these are in their early stages, but the encouraging promise of this cell therapy will ensure more trials to come. This review will first discuss MSCs as a population with varied properties and mechanisms of action and then will examine the efforts so far to use MSCs as treatment in various lung diseases.

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Mesenchymal stem cells transplantation protects against rat pulmonary emphysema

Cited by 111 publications

References 22 publications

Stem Cell Treatment for Chronic Lung Diseases

Stem Cell Treatment for Chronic Lung Diseases

Therapeutic Effects of Human Mesenchymal Stem Cells in Ex Vivo Human Lungs Injured with Live Bacteria

Mesenchymal stem cells for therapy in lung diseases

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