Inhaled Placental Mesenchymal Stromal Cell Secretome from Two- and Three-Dimensional Cell Cultures Promotes Survival and Regeneration in Acute Lung Injury Model in Mice

Kudinov, V.A.; Artyushev, Rafael I.; Зурина, И.М.; Zorina, Elena; Lapshin, R.D.; Snopova, Ludmila B.; Мухина, И.В.; Сабурина, И.Н.

doi:10.3390/ijms23073417

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…The in vitro anti-inflammatory results revealed that the synergy between HA and secretome exerts preventive anti-inflammatory beneficial effects exhibiting regenerative properties. This behavior may be explained considering the beneficial effect of secretome and HA in the modulation of the inflammatory response [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Hyaluronic Acid and Mesenchymal Stem Cells Secretome Combination in Promoting Alveolar Regeneration

Sala

Longobardo

Lista

et al. 2023

IJMS

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Pharmacological therapies in lung diseases are nowadays useful in reducing the symptomatology of lung injury. However, they have not yet been translated to effective treatment options able to restore the lung tissue damage. Cell-therapy based on Mesenchymal Stem Cells (MSCs) is an attractive, as well as new therapeutic approach, although some limitations can be ascribed for therapeutic use, such as tumorigenicity and immune rejection. However, MSCs have the capacity to secrete multiple paracrine factors, namely secretome, capable of regulating endothelial and epithelial permeability, decrease inflammation, enhancing tissue repair, and inhibiting bacterial growth. Furthermore, Hyaluronic Acid (HA) has been demonstrated to have particularly efficacy in promoting the differentiation of MSCs in Alveolar type II (ATII) cells. In this frame, the combination of HA and secretome to achieve the lung tissue regeneration has been investigated for the first time in this work. Overall results showed how the combination of HA (low and medium molecular weight HA) plus secretome could enhance MSCs differentiation in ATII cells (SPC marker expression of about 5 ng/mL) compared to the only HA or secretome solutions alone (SPC about 3 ng/mL, respectively). Likewise, cell viability and cell rate of migration were reported to be improved for HA and secretome blends, indicating an interesting potentiality of such systems for lung tissue repair. Moreover, an anti-inflammatory profile has been revealed when dealing with HA and secretome mixtures. Therefore, these promising results can allow important advance in the accomplishment of the future therapeutic approach in respiratory diseases, up to date still missing.

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Section: Discussionmentioning

confidence: 99%

Effect of Hyaluronic Acid and Mesenchymal Stem Cells Secretome Combination in Promoting Alveolar Regeneration

Sala

Longobardo

Lista

et al. 2023

IJMS

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“…Moreover, MSCs immunosuppress inflammatory response in the early phase of tissue injury, resulting in less scarring and tissue regeneration ( 30 ). The immunomodulatory properties of MSCs also rely on the paracrine effects, including cytokines and extracellular vesicles ( 31 , 32 ). Emerging evidence has demonstrated that MSC-derived exosomes have immunomodulatory functions similar to those of donor MSCs ( 33 – 35 ).…”

Section: Discussionmentioning

confidence: 99%

Global scientific trends on the immunomodulation of mesenchymal stem cells in the 21st century: A bibliometric and visualized analysis

et al. 2022

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BackgroundSince the discovery of the immunomodulatory functions of mesenchymal stem cells (MSCs), their application in immunomodulation has attracted considerable attention, and an increasing number of studies have been conducted worldwide. Our research aimed to investigate the global status and trends in this field.MethodsPublications on the immunomodulatory functions of MSCs from 1 January 2000 to 7 March 2022 were retrieved from the Web of Science Core Collection. The data were studied and indexed using the bibliometric methodology. Visualization analysis, co-authorship, co-occurrence analysis, and publication trends in MSC immunomodulation were conducted using the VOSviewer software.ResultsIn total, 4,227 papers were included in the study. The number of publications and research interests has significantly increased globally. China published the highest number of related articles, while the US published articles with the highest number of citations. Stem Cell Research & Therapy had the highest number of publications. Sun Yat-sen University, Shanghai Jiao Tong University, Harvard University, and Seoul National University were the most contributive institutions. Furthermore, the studies were divided into four research hotspots for MSC immunomodulation: MSC immunomodulation in regenerative medicine, the effects and mechanisms of MSC immunomodulation, MSC therapy for immune diseases, and the cell source of MSCs.ConclusionThis study indicates that the number of publications on MSC immunomodulation will increase in the future, and MSC immunomodulation mechanisms and clinical applications of MSC immunotherapy should be the next hotspots in this research field.

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“…In the experiment, an inhalation system of an original design was used, which allows simultaneously accommodating 1 or up to 10 small laboratory animals. The system recognizes oneself as a sealed chamber for animals with a nebulizer, inlet pipes into the chamber, and outlet pipes from the chamber, equipped with special degassing traps [ 29 ]. The LPS simulating the ALI dose was 10 mg/kg with an air supply of 2 L/h per animal with an exposure of 90 min (0.16 L/min).…”

Section: Methodsmentioning

confidence: 99%

Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model

Markin

Lapshin

Baskina

et al. 2022

IJMS

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Acute lung injury (ALI) as a model of acute respiratory distress syndrome is characterized by inflammation, complex coagulation, and hematologic abnormalities which result in the formation of fibrin-platelet microthrombi in the pulmonary vessels with the rapid development of progressive respiratory dysfunction. We hypothesize that a nebulized fibrinolytic agent, non-immunogenic staphylokinase (nSta), may be useful for ALI therapy. First, the effect of the nebulized nSta (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg) on the coagulogram parameters was studied in healthy rats. ALI was induced in mice by nebulized administration of lipopolysaccharide (LPS) at a dose of 10 mg/kg. nSta (0.2 mg/kg, 0.4 mg/kg or 0.6 mg/kg) was nebulized 30 min, 24 h, and 48 h after LPS administration. The level of pro-inflammatory cytokines was determined in the blood on the 8th day after LPS and nSta administration. The assessment of lung damage was based on their weighing and microscopic analysis. Fibrin/fibrinogen deposition in the lungs was determined by immunohistochemistry. After nSta nebulization in healthy rats, the fibrinogen blood level as well as activated partial thromboplastin time and prothrombin time did not change. In the nebulized ALI model, the mice showed an increase in lung weight due to their edema and rising fibrin deposition. An imbalance of proinflammatory cytokines was also found. Forty percent of mice with ALI without nSta nebulization had died. Nebulized nSta at a dose of 0.2 mg/kg reduced the severity of ALI: a decrease in interstitial edema and inflammatory infiltration was noted. At a dose of 0.4 mg/kg of nebulized nSta, the animals showed no peribronchial edema and the bronchi had an open clear lumen. At a dose of 0.6 mg/kg of nebulized nSta, the manifestations of ALI were completely eliminated. A significant dose-dependent reduction of the fibrin-positive areas in the lungs of mice with ALI was established. Nebulized nSta had a normalizing effect on the proinflammatory cytokines in blood— interleukin (IL)-1α, IL-17A, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). These data showed the effectiveness of nebulized nSta and the perspectives of its clinical usage in COVID-19 patients with acute respiratory distress syndrome (ARDS).

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Inhaled Placental Mesenchymal Stromal Cell Secretome from Two- and Three-Dimensional Cell Cultures Promotes Survival and Regeneration in Acute Lung Injury Model in Mice

Cited by 9 publications

References 53 publications

Effect of Hyaluronic Acid and Mesenchymal Stem Cells Secretome Combination in Promoting Alveolar Regeneration

Effect of Hyaluronic Acid and Mesenchymal Stem Cells Secretome Combination in Promoting Alveolar Regeneration

Global scientific trends on the immunomodulation of mesenchymal stem cells in the 21st century: A bibliometric and visualized analysis

Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model

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