scholarly journals Mesenchymal Stromal Cells for the Treatment of Interstitial Lung Disease in Children: A Look from Pediatric and Pediatric Surgeon Viewpoints

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3270
Author(s):  
Gloria Pelizzo ◽  
Serena Silvestro ◽  
Maria Antonietta Avanzini ◽  
Gianvincenzo Zuccotti ◽  
Emanuela Mazzon ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Age Of Onset ◽  
Point Of View ◽  
High Morbidity ◽  
Severe Toxicity ◽  
Adult Age ◽  
Pulmonary Parenchyma

Mesenchymal stromal cells (MSCs) have been proposed as a potential therapy to treat congenital and acquired lung diseases. Due to their tissue-regenerative, anti-fibrotic, and immunomodulatory properties, MSCs combined with other therapy or alone could be considered as a new approach for repair and regeneration of the lung during disease progression and/or after post- surgical injury. Children interstitial lung disease (chILD) represent highly heterogeneous rare respiratory diseases, with a wild range of age of onset and disease expression. The chILD is characterized by inflammatory and fibrotic changes of the pulmonary parenchyma, leading to gas exchange impairment and chronic respiratory failure associated with high morbidity and mortality. The therapeutic strategy is mainly based on the use of corticosteroids, hydroxychloroquine, azithromycin, and supportive care; however, the efficacy is variable, and their long-term use is associated with severe toxicity. The role of MSCs as treatment has been proposed in clinical and pre-clinical studies. In this narrative review, we report on the currently available on MSCs treatment as therapeutical strategy in chILD. The progress into the therapy of respiratory disease in children is mandatory to ameliorate the prognosis and to prevent the progression in adult age. Cell therapy may be a future therapy from both a pediatric and pediatric surgeon’s point of view.

scholarly journals Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Martina Sandonà ◽  
Lorena Di Pietro ◽  
Federica Esposito ◽  
Alessia Ventura ◽  
Antonietta Rosa Silini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Muscle Regeneration ◽  
Point Of View ◽  
Biologically Active ◽  
Therapeutic Interventions ◽  
Skeletal Muscle Regeneration ◽  
Therapeutic Effects ◽  
Muscular Diseases

Mesenchymal stromal cells (MSCs) are multipotent cells found in different tissues: bone marrow, peripheral blood, adipose tissues, skeletal muscle, perinatal tissues, and dental pulp. MSCs are able to self-renew and to differentiate into multiple lineages, and they have been extensively used for cell therapy mostly owing to their anti-fibrotic and immunoregulatory properties that have been suggested to be at the basis for their regenerative capability. MSCs exert their effects by releasing a variety of biologically active molecules such as growth factors, chemokines, and cytokines, either as soluble proteins or enclosed in extracellular vesicles (EVs). Analyses of MSC-derived secretome and in particular studies on EVs are attracting great attention from a medical point of view due to their ability to mimic all the therapeutic effects produced by the MSCs (i.e., endogenous tissue repair and regulation of the immune system). MSC-EVs could be advantageous compared with the parental cells because of their specific cargo containing mRNAs, miRNAs, and proteins that can be biologically transferred to recipient cells. MSC-EV storage, transfer, and production are easier; and their administration is also safer than MSC therapy. The skeletal muscle is a very adaptive tissue, but its regenerative potential is altered during acute and chronic conditions. Recent works demonstrate that both MSCs and their secretome are able to help myofiber regeneration enhancing myogenesis and, interestingly, can be manipulated as a novel strategy for therapeutic interventions in muscular diseases like muscular dystrophies or atrophy. In particular, MSC-EVs represent promising candidates for cell free-based muscle regeneration. In this review, we aim to give a complete picture of the therapeutic properties and advantages of MSCs and their products (MSC-derived EVs and secreted factors) relevant for skeletal muscle regeneration in main muscular diseases.

scholarly journals Coexistence of Axial Spondyloarthritis and Idiopathic Inflammatory Myopathy

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Yongpeng Ge ◽  
Linrong He
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Skin Rash ◽  
Axial Spondyloarthritis ◽  
Age Of Onset ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Hla B27 ◽  
Laboratory Features ◽  
Friendship Hospital

Both axial spondyloarthritis (axSpA) and idiopathic inflammatory myopathy (IIM) are infrequent, and their coexistence is even rarer; there are a few reported cases in the literature. The aim of this study was to assess their association and clinical and laboratory features in our patients. The clinical data of patients with axSpA and IIM diagnosed in China-Japan Friendship Hospital from July 2015 to February 2019 were retrospectively analyzed. This study included 7 patients with axSpA who met the IIM criteria, including 3 males and 4 females. The age of onset was 16 to 39 years. Four patients were HLA-B27 positive, and three were negative. All patients were first diagnosed as axSpA, and then IIM was detected after 0.5–20 years (mean ± SD, 9.9 ± 5.0 years). After being diagnosed to have axSpA and IIM, those patients were given prednisone and immunosuppressant drugs, and their symptoms gradually improved. Our study provides further evidence of the coexistence of IIM with axSpA. In patients with axSpA who have skin rash, interstitial lung disease (ILD), myalgia, or muscle weakness, we should suspect that they may have IIM.

scholarly journals The Value of Effective Lung Ventilation Area Ratio Based on CT Image Analysis Is a New Index to Predict the Shorter Outcome of Anti-melanoma Differentiation-Associated Protein 5 Positive Dermatomyositis Associated Interstitial Lung Disease: A Single-Center Retrospective Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Changjian Wang ◽  
Jinfeng Du ◽  
Xilong Mei ◽  
Lingchao Guo ◽  
Fangzhao Li ◽  
...  
Keyword(s):  
Image Analysis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Age Of Onset ◽  
Lung Ventilation ◽  
Early Death ◽  
Survival Group ◽  
Early Survival ◽  
Poor Outcomes ◽  
Death Group

Background: Anti-melanoma differentiation-associated protein 5 (MDA5) positive dermatomyositis (MDA5+DM) patients have poor outcomes due to rapidly progressive interstitial lung disease (ILD). The accurate assessment of lung involvement is an urgent focus of research.Methods: A computer-aided lung interstitial image analysis technology has been developed, and a quantitative indicator named effective lung ventilation area ratio (ELVAR) that calculates the proportion of the area outside the lung interstitium in lung tissue has been established. 55 newly diagnosed MDA5+DM patients and 46 healthy individuals, matched for age and gender, were enrolled in this study. MDA5+DM patients were classified into early death group or early survival group according to their survival state within 3 months after diagnosis. Clinical characteristics, laboratory and immunological test results, lung involvement (including ELVAR value) and treatment were compared between early death group and early survival group to determine an index that can predict prognoses of patients with MDA5+DM.Results: There were significant differences between early death MDA5+DM patients and early survival MDA5+DM patients about 12 indices including age of onset, CRP, ferritin, albumin, and pulmonary involvement including severity of type I respiratory failure at diagnosis, P/F ratio, oxygen supplementation, values of ELVAR, FVC, and DLCO. The results of ROC analysis and correlation analysis showed the value of ELVAR had good diagnostic value and widely correlation with many clinical characteristics. Univariate analysis and Multivariate analysis showed four factors including age of onset, ferritin, value of ELVAR, and oxygen supplementation >4 L/min significantly value for poor prognosis in MDA5+DM patients. A cutoff value of 0.835 about ELVAR had good predictive power for mortality within 3 months in 54.2% of MDA5+DM patients.Conclusion: The value of ELVAR derived from computed tomography image analysis is a new index that can predict poor outcomes in MDA5+DM patients with rapidly progressive interstitial lung disease.

Clinical, Radiological And Laboratory Predictors Of Postcovid Interstitial Pulmonary Disease

2021 ◽  
Vol 03 (08) ◽  
pp. 26-36
Author(s):  
Anvar Dalimov Arabboyevich ◽  
◽  
Dilfuzahon Mamarasulova Zakirjanovna ◽  
Nodirbek Ilkhomjon Ogli Yakubov ◽  
◽  
...  
Keyword(s):  
Risk Assessment ◽  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Assessment Scale ◽  
Pulmonary Parenchyma ◽  
Interstitial Pulmonary Disease

The Fergana Valley model was used to study the risk of postcovid interstitial lung disease in patients who have had COVID-19 associated pneumonia with 50% or more of the pulmonary parenchyma affected. Predictors of the formation of postcovid pulmonary fibrosis were determined and a risk assessment scale was developed. It was found that the use of ultrasound scanners in the early postcovid period is informative and is not inferior in terms of predicting fibrosis by serial MSCT.

scholarly journals OP0249 SERUM PROTEOMIC BIOMARKERS DEFINE PATIENTS WITH SYSTEMIC SCLEROSIS WITH INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 152.2-152
Author(s):  
M. De Santis ◽  
N. Isailovic ◽  
A. Ceribelli ◽  
F. Motta ◽  
M. Vecellio ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Proteomic Analysis ◽  
Organ Involvement ◽  
High Morbidity ◽  
Healthy Controls ◽  
Altered Expression ◽  
Calgranulin B ◽  
Angiopoietin 2

Background:Systemic sclerosis (SSc) is a systemic condition affecting multiple organs and thus being burdened by high morbidity and mortality; disease management is based largely on the early detection of organ involvement, particularly in the case of interstitial lung disease (ILD), ideally through noninvasive biomarkers. Beside serum autoantibodies associated with diffuse SSc, there is currently no reliable serum marker to predict the onset of SSc organ involvement, monitor its progression, and foresee the response to treatments. Proteomic analysis based on aptamer technology is a powerful method with the potential to address this unmet need in SSc.Objectives:To identify serum biomarkers associated with ILD in SSc.Methods:Serum samples from 6 women with SSc (3 with ILD at high-resolution pulmonary CT scan) and 7 age-matched female healthy controls (HC) were analyzed using the SOMAscan platform (SomaLogic, Inc., Boulder, CO, USA) to test more than 1300 proteins even at femtomolar concentration. Subsequent validation of candidate proteins was performed using ELISA in an independent cohort of 88 patients with SSc and 48 HC. Statistical analysis included Student’s t-test and was assessed using the SomaSuite software (SomaLogic, Boulder, CO, USA).Results:The proteomic analysis identified 33 proteins with significantly different serum levels in SSc cases compared to HC and 9 proteins differentiating SSc patients according to ILD (Table 1). Compared to HC, SSc sera manifested an altered expression of proteins involved in extracellular matrix formation and cell-cell adhesion (with higher Calpain, EphA5, IDS, MATN2, MMP-12, TNR4, and lower desmoglein-1, SNP25), angiogenesis (with higher anti-angiogenetic factors as angiopoietin-2 and kininogen high molecular weight) lymphocyte recruitment, activation, and signaling (with higher CXCL-1, LAG3 and lower SH21A) with an overall inhibition of neutrophil function (with lower G-CSF-R, CD177, calgranulin B).Table 1.Significantly altered proteins at serum proteomic analysis of systemic sclerosis (SSc) with or without interstitial lung disease (ILD) and healthy controls (HC)SSc versus healthy controlsSSc with ILD versus SSc without ILD and healthy controlsIncreasedReducedIncreasedReducedAldolase AAngiopoietin-2*C1QR1CalpainCOLEC12 EotaxinEphA5Fractalkine/CXCL-1GranulinsIDS Kininogen, HMVLAG-3Lamin-B1LRP1bMATN2MMP-12STAT1 TMR4AdrenomedullinASGR1C1sC5Calgranulin BCD177Desmoglein-1Flt-3 ligandG-CFS-RIL-1RaLeptinLypd3SH21ASNP25TPBS2FCRL3IL-22BP**MCP-3PDE11PGP9.5sICAM-5StratifinBAFFDERM*significantly increased also at ELISA** significantly increased at ELISA only in SSc with ILD versus HCThe majority of proteins with higher levels in SSc with ILD compared to SSc without ILD were involved in intracellular signaling and cell cycle (FCRL3, PDE11, Stratifin), along with higher MCP-3, a monocyte chemoattractant, and sICAM-5, ligand for the leukocyte adhesion protein LFA-1. Of note, we found that increased IL-22BP, antagonist of IL-22, and decreased BAFF levels characterized SSc with ILD.Conclusion:Aptamer proteomic analysis allowed to define serum profiles differentiating SSc patients from healthy controls and SSc with ILD from SSc without ILD; the proteins identified are involved in SSc pathogenic pathways and after further investigation on larger cohorts they can be used as reliable biomarkers.Characters from table content including title and footnotes: 631Disclosure of Interests:None declared

scholarly journals Myositis-Related Interstitial Lung Disease: A Respiratory Physician’s Point of View

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 599
Author(s):  
Yuko Waseda
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Unknown Origin ◽  
Trna Synthetase ◽  
Point Of View ◽  
Aminoacyl Trna Synthetase ◽  
Inflammatory Myositis ◽  
Idiopathic Inflammatory Myositis ◽  
Inflammatory Drugs

Idiopathic inflammatory myositis (IIM) is an umbrella term for diseases of unknown origin that cause muscle inflammation. Dermatomyositis and polymyositis are IIMs that commonly cause interstitial lung disease (ILD). When a patient presents with ILD, the evaluation of whether the case displays the characteristics of myositis should be determined by interview, physical examination, imaging findings, the measurement of myositis-related antibodies, and the determination of disease severity after diagnosis. Rapidly progressing anti-melanoma differentiation-associated gene 5 antibody-positive ILD may require rapid multi-drug therapy, while anti-aminoacyl tRNA synthetase (ARS) antibody-positive ILD can be treated with anti-inflammatory drugs. Importantly, however, anti-ARS antibody-positive ILD often recurs and sometimes develops into fibrosis. Early diagnosis is crucial for treatment, and we therefore need to clarify the features of myositis associated with ILD and suspect these pathologies early. This section reviews what clinicians need to look for and what findings are evaluated in patients when diagnosing myositis associated with ILD.

scholarly journals High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Albina Tyker ◽  
Iazsmin Bauer Ventura ◽  
Cathryn T. Lee ◽  
Rachel Strykowski ◽  
Nicole Garcia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Rheumatoid Factor ◽  
Cox Regression ◽  
Mediastinal Lymph Node ◽  
High Titer ◽  
Mediastinal Lymphadenopathy ◽  
High Morbidity

AbstractRheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36 months among patients who had high-titer RF seropositivity (≥ 60 IU/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1–6.8; P = 0.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.

scholarly journals Role of ex vivo Expanded Mesenchymal Stromal Cells in Determining Hematopoietic Stem Cell Transplantation Outcome

2021 ◽  
Vol 9 ◽  
Author(s):  
Stefania Crippa ◽  
Ludovica Santi ◽  
Margherita Berti ◽  
Giada De Ponti ◽  
Maria Ester Bernardo
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Late Complications ◽  
Point Of View ◽  
Human Organism ◽  
Paracrine Factors ◽  
Hematopoietic Stem ◽  
Bm Niche ◽  
The One

Overall, the human organism requires the production of ∼1 trillion new blood cells per day. Such goal is achieved via hematopoiesis occurring within the bone marrow (BM) under the tight regulation of hematopoietic stem and progenitor cell (HSPC) homeostasis made by the BM microenvironment. The BM niche is defined by the close interactions of HSPCs and non-hematopoietic cells of different origin, which control the maintenance of HSPCs and orchestrate hematopoiesis in response to the body’s requirements. The activity of the BM niche is regulated by specific signaling pathways in physiological conditions and in case of stress, including the one induced by the HSPC transplantation (HSCT) procedures. HSCT is the curative option for several hematological and non-hematological diseases, despite being associated with early and late complications, mainly due to a low level of HSPC engraftment, impaired hematopoietic recovery, immune-mediated graft rejection, and graft-versus-host disease (GvHD) in case of allogenic transplant. Mesenchymal stromal cells (MSCs) are key elements of the BM niche, regulating HSPC homeostasis by direct contact and secreting several paracrine factors. In this review, we will explore the several mechanisms through which MSCs impact on the supportive activity of the BM niche and regulate HSPC homeostasis. We will further discuss how the growing understanding of such mechanisms have impacted, under a clinical point of view, on the transplantation field. In more recent years, these results have instructed the design of clinical trials to ameliorate the outcome of HSCT, especially in the allogenic setting, and when low doses of HSPCs were available for transplantation.

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