• B cell differentiation
• Crohn's disease
• inflammation
• memory B cells
• plasma cells
• scBCR-seq
• scRNA-seq

• National Natural Science Foundation of China
• National Key Research and Development Program of China
• ‘Pioneer’ and ‘Leading Goose’ R&D Program of Zhejiang
• HRHI program of Westlake Laboratory of Life Sciences and Biomedicine
• Westlake University

• leucine-rich repeat-containing G-protein-coupled receptor 4
• osteoclasts
• osteoporosis
• osteoprotegerin
• receptor activator of nuclear factor kappa-B ligand

• NRF- 2023M3A9J4057906, RS-2023-00217471 National Research Foundation of Korea (NRF)

• Animal model
• Rat
• Ultrasound
• Urethral stricture

• Animals
• Urethral Stricture/diagnostic imaging
• Urethral Stricture/pathology
• Urethral Stricture/therapy
• Male
• Disease Models, Animal
• Rats
• Rats, Sprague-Dawley
• Ultrasonography/methods
• Urethra/diagnostic imaging
• Urethra/pathology
• Transforming Growth Factor beta1

• BPB-2022YXJ Provincial subsidy fund for health and wellness from Fujian Provincial Department of Finance
• 2020GGB032 Fujian Provincial Health Technology Project

• Muscle, Skeletal/metabolism
• Muscle, Skeletal/cytology
• Paracrine Communication
• Animals
• Printing, Three-Dimensional
• Mice
• Oxygen/metabolism
• Cell Line
• Myoblasts/cytology
• Myoblasts/metabolism
• Cell Hypoxia
• Tissue Engineering
• Microphysiological Systems

• K99 HL157722 NHLBI NIH HHS
• R01 CA220012 NCI NIH HHS
• R01 HL153286 NHLBI NIH HHS
• R25 DK113652 NIDDK NIH HHS

• Andiz
• Gene expression
• IL-1β
• TGF-β
• Wound healing
• β-actin

• Animals
• Wound Healing/drug effects
• Wound Healing/genetics
• Rats
• Male
• Rats, Wistar
• Plant Extracts/pharmacology
• Chlorhexidine/pharmacology
• Chlorhexidine/analogs & derivatives
• Interleukin-1beta/genetics
• Interleukin-1beta/metabolism
• Anti-Bacterial Agents/pharmacology
• Gene Expression/drug effects
• DNA, Bacterial/genetics

• exosomes
• immune cells
• immunomodulation
• inflammation
• mesenchymal stem cells
• pulmonary disease

• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/immunology
• COVID-19/immunology
• COVID-19/therapy
• Lung/immunology
• Lung/pathology
• SARS-CoV-2/immunology
• Lung Diseases/immunology
• Lung Diseases/therapy
• Animals
• Cell Differentiation
• Cell Communication/immunology

• bone marrow-derived mesenchymal stromal cells (BM-MSCs)
• emphysema
• lung volume reduction surgery (LVRS)
• mass cytometry by-time-of-flight (CyTOF)
• pulmonary immune profile
• systemic immune profile

• Humans
• Mesenchymal Stem Cell Transplantation/methods
• Male
• Female
• Lung/pathology
• Lung/immunology
• Mesenchymal Stem Cells/immunology
• Mesenchymal Stem Cells/cytology
• Middle Aged
• Pulmonary Emphysema/immunology
• Pulmonary Emphysema/surgery
• Pulmonary Emphysema/therapy
• Aged
• Pneumonectomy
• Transplantation, Homologous

• 0414009816007) Netherlands Organisation for Health Research and Development
• 201906170073 Chinese Scholarship council

• BMMSC
• TNF-α
• mitophagy
• quiescence
• succinylation

• Tumor Necrosis Factor-alpha/metabolism
• Mitophagy
• Mesenchymal Stem Cells/metabolism
• Cell Differentiation

• RCYX20210706092106042 Shenzhen Science and Technology Program
• FTWS2022016 Futian Healthcare Research Project
• 2023A1515030026 Guangdong Natural Science Foundation
• 82272448 National Natural Science Foundation of China
• 82172349 National Natural Science Foundation of China
• 82172385 National Natural Science Foundation of China
• Guangdong Natural Science Foundation
• National Natural Science Foundation of China

• Th-17 cells
• UC-MSCs
• immunomodulation
• inflammation
• tissue repair

• Interleukin-17
• Th17 Cells
• Mesenchymal Stem Cells
• Coculture Techniques
• Immunomodulation

• NA Generation Life Foundation
• NA Fonds Lambeau-Marteaux
• NA Fonds National de la Recherche Scientifique
• NA PDR
• NA Télévie
• NA Les Amis de l'Institut Jules Bordet
• NA La Chaire en Arthrose de l'Université de Montréal
• SOG-20-0000000046 The Arthritis Society
• PJT 175-1110 The Canadian Institutes of Health Research
• NA Centre National pour la Recherche Scientifique et Technique
• NA L'Agence Nationale des Plantes Médicinales et Aromatiques

• Adenomyosis
• Endometrial repair
• Glycolysis
• Heavy menstrual bleeding
• Hypoxia
• Mouse

• RTqPCR
• gene
• spinal stenosis
• surgical treatment
• tethered cord syndrome
• transforming growth factor β
• wound healing

• TNF-α
• exosomal microvesicles
• immunomodulation
• mesenchymal stem cells
• tissue regeneration and repair

• Angiogenesis
• LPS
• MSCs
• VEGF
• Wound healing

Mesenchymal stem cells (MSCs) secrete paracrine factors and extracellular matrix proteins that contribute to their ability to support tissue healing and regeneration. Both the transcriptome and the secretome of MSCs can be altered by treating the cells with cytokines, but neither have been thoroughly investigated following treatment with the specific cytokine transforming growth factor (TGF)-β2.

RNA-sequencing and western blotting were used to compare gene and protein expression between untreated and TGF-β2-treated equine bone marrow-derived MSCs (BM-MSCs). A co-culture system was utilized to compare equine tenocyte migration during co-culture with untreated and TGF-β2-treated BM-MSCs.

TGF-β2 treatment significantly upregulated gene expression of collagens, extracellular matrix molecules, and growth factors. Protein expression of collagen type I and tenascin-C was also confirmed to be upregulated in TGF-β2-treated BM-MSCs compared to untreated BM-MSCs. Both untreated and TGF-β2-treated BM-MSCs increased tenocyte migration in vitro.

Treating equine BM-MSCs with TGF-β2 significantly increases production of paracrine factors and extracellular matrix molecules important for tendon healing and promotes the migration of tenocytes in vitro.

The online version contains supplementary material available at 10.1186/s13287-022-03172-9.

• K01 OD027037 NIH HHS
• Grayson-Jockey Club Research Foundation
• National Institutes of Health

Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, are one of the most frequent causes of morbidity and mortality in the global. COPD is characterized by progressive loss of lung function through inflammation, apoptosis, and oxidative stress caused by chronic exposure to harmful environmental pollutants. Airway inflammation and epithelial remodeling are also two main characteristics of asthma. In spite of extensive efforts from researchers, there is still a great need for novel therapeutic approaches for treatment of these conditions. Accumulating evidence suggests the potential role of mesenchymal stem cells (MSCs) in treatment of many lung injuries due to their beneficial features including immunomodulation and tissue regeneration. Besides, the therapeutic advantages of MSCs are chiefly related to their paracrine functions such as releasing extracellular vesicles (EVs). EVs comprising exosomes and microvesicles are heterogeneous bilayer membrane structures loaded with various lipids, nucleic acids and proteins. Due to their lower immunogenicity, tumorigenicity, and easier management, EVs have appeared as favorable alternatives to stem cell therapies. Therefore, in this review, we provided an overview on the current understanding of the importance of MSCs and MSC-derived EVs from different sources reported in preclinical and clinical COPD and asthmatic models.

• Asthma
• COPD
• Emphysema
• Exosomes
• Lung diseases
• Mesenchymal stromal cells
• Microvesicles
• Regeneration

• Health Commission of Sichuan Province
• Sichuan Science & Technology Department
• Chengdu Science and Technology Bureau

Wound repair is accomplished by the interaction between the cells involved in the repair and the extracellular matrix (ECM). Collagen is the main component of ECM, which is involved in transduction of signal, transportation of growth factors and cytokines. Fibronectin (FN) is also an important ECM, which participates in the initiation of fibroblast cell (FC) and promotes adhesion, migration, proliferation and differentiation of target cells. Compared with natural protein, the recombinant protein prepared by artificial method has the advantages of poor immunogenicity, wide range of sources, low cost and high activity. In this study, we used recombinant human-like collagen (RHC) and recombinant human-like fibronectin (rhFN) to treat acute wounds in C57BL/6 mice individually or in combination, and explored their effects on wound healing. Our study confirmed that these two recombinant proteins could effectively promote the proliferation, migration and adhesion of FCs. Meanwhile, it could positively regulate the healing speed and quality of acute wounds, re-epithelialization, collagen deposition, inflammation and angiogenesis. Moreover, we proved that the combination of the two was better than the treatment alone. Consequently, it has a good prospect as a new tissue material in the field of skin repair.

• BEAS-2B
• Lung injury
• MicroRNA
• Mouse
• PM2.5
• U937

• Humans
• Inflammation/genetics
• Lung/metabolism
• Lung Injury/chemically induced
• Lung Injury/genetics
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Particulate Matter/toxicity

• COPD
• cell therapy
• co-infusion
• concomitant infusion
• mesenchymal stem cells
• stem cells

• Bone Marrow
• Forced Expiratory Volume
• Humans
• Mesenchymal Stem Cells
• Pulmonary Disease, Chronic Obstructive/drug therapy
• Pulmonary Disease, Chronic Obstructive/therapy
• Quality of Life

• the National Council for Scientific and Technological Development –CNPq – Brazil

• King Saud University

• Acute appendicitis
• Endoscopic retrograde appendicitis therapy
• Laparoscopic appendectomy
• Meta analysis
• Randomized controlled study

• COPD
• MSCs
• alveolar epithelium
• cell therapy
• emphysema
• growth factors
• lung repair
• organoids
• regenerative medicine

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.

• ARDS
• COVID-19
• MSCs therapies
• SARS-CoV-2
• sepsis

• IL-6
• MAPK signaling pathway
• STAT3
• TNF-α
• acute lung injury
• acute respiratory distress syndrome
• corylin

• 3D models
• Cell culture
• Co-culture
• Drug absorption
• Inhalation
• Isolated and perfused lung
• Membrane transporters
• Precision-cut lung slices
• Pulmonary drug delivery

The 21st century already witnessed many deadly epidemics and pandemics. The major ones were respiratory tract infections like SARS (2003), H1N1 (2009), MERS (2012) and the most recent pandemic COVID-19 (2019). The COVID-19 story begins when pneumonia of unknown cause was reported in the WHO country office of China at the end of 2019. SARS-CoV-2 is the causative agent that enters the host through the receptor ACE2, a component of the renin–angiotensin system.

Symptoms of COVID-19 varies from patient to patient. It is all about the immunity and health status of the individual that decides the severity of the disease. The review focuses on the significant and often prevailing factors, those that influence the lung function. The factors that compromise the lung functions which may prepare the ground for severe COVID-19 infection are interestingly looked into. Focus was more on air pollution and cigarette smoke.

The fact that the forested areas across the world show very low COVID-19 infection rate suggests that we are in need of the “Clean Air” on the fiftieth anniversary of World Earth Day. As many policies are implemented worldwide to protect from SARS-CoV-2, one simple remedy that we forgot was clean air can save lives. SARS-CoV-2 infects our lungs, and air pollution makes us more susceptible. In this crucial situation, the focus is only on the main threat; all other conditions are only in words to console the situation.

• Animals
• Diabetes Mellitus, Experimental
• Female
• Hepatocyte Growth Factor/genetics
• Humans
• Male
• Mesenchymal Stem Cells
• Rats
• Rats, Sprague-Dawley
• Vascular Endothelial Growth Factor A
• Wound Healing

• 81871561 General Program of National Natural Science Foundation of China
• 82002039 Youth Science Foundation of National Natural Science Foundation of China

• acute respiratory distress syndrome
• asthma
• chronic obstructive pulmonary disease
• idiopathic pulmonary fibrosis
• mesenchymal stem cells

• National Natural Science Foundation of China

• Endothelial Progenitor Cells
• Immunoregulation
• Immunosuppression
• Mesenchymal Stem Cells
• T cells
• TNFα-TNFR2 signaling pathway

• exosomes
• let-7c
• mesenchymal stem cells
• polarization of macrophages
• urethral stricture

The therapeutic value of mesenchymal stem cells (MSCs) for the treatment of infectious diseases and the repair of disease-induced tissue damage has been explored extensively. MSCs inhibit inflammation, reduce pathogen load and tissue damage encountered during infectious diseases through the secretion of antimicrobial factors for pathogen clearance and they phagocytose certain bacteria themselves. MSCs dampen tissue damage during infection by downregulating the levels of pro-inflammatory cytokines, and inhibiting the excessive recruitment of neutrophils and proliferation of T cells at the site of injury. MSCs aid in the regeneration of damaged tissue by differentiating into the damaged cell types or by releasing paracrine factors that direct tissue regeneration, differentiation, and wound healing. In this review, we discuss in detail the various mechanisms by which MSCs help combat pathogens, tissue damage associated with infectious diseases, and challenges in utilizing MSCs for therapy.

• Infectious diseases
• Mesenchymal stem cells
• Antimicrobial effect
• Immunomodulation
• Tissue repair
• COVID-19

Tissue factor (TF) plays an important role in the progression and angiogenesis of tumor cells. The present study investigated the mechanism of interleukin-1β (IL-1β)-induced TF expression in A549 lung cancer cells. Based on mRNA and protein analyses, including appropriate inhibitor experiments, IL-1β was shown to induce TF expression in a time-dependent manner, mediated by IL-1 receptor-dependent phosphorylation of the mitogen-activated protein kinases (MAPK) p38, p42/44 and c-jun N-terminal kinase (JNK), as well as the Src kinase and the epidermal growth factor receptor (EGFR). Thereby, inhibition of EGFR transactivation by the Src inhibitor PP1 or direct EGFR inhibition by the EGFR tyrosine kinase inhibitor (TKI) erlotinib led to a reduction of IL-1β-induced TF expression and to a suppression of p42/44 MAPK and EGFR activation, while IL-1β-induced p38 MAPK and JNK activation remained unchanged. A knockdown of EGFR by siRNA was associated with decreased IL-1β-mediated p42/44 MAPK activation, which was no longer inhibitable by erlotinib. Concentration-dependent inhibition of IL-1β-induced TF expression was also observed in the presence of gefitinib and afatinib, two other EGFR TKIs. In summary, our results suggest that IL-1β leads to increased TF formation in lung cancer cells via both Src/EGFR/p42/44 MAPK-dependent and EGFR-independent signaling pathways, with the latter mediated via p38 MAPK and JNK.

• epidermal growth factor receptor
• erlotinib
• interleukin-1β
• lung cancer cells
• mitogen-activated protein kinases
• tissue factor

• A549 Cells
• ErbB Receptors/metabolism
• Humans
• Interleukin-1beta/metabolism
• MAP Kinase Signaling System
• Thromboplastin/metabolism

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.

• bone marrow niche
• hematopoietic (stem) cell transplantation
• hematopoietic stem and progenitor cell
• immunoregulation
• mesenchymal stromal cells

• MSCs
• emphysema
• extracellular matrix
• growth factors
• lung tissue repair

Aim of the study: Both nasal and bronchial epithelial cells have evolved sophisticated mechanisms involved in cellular response to bacterial infection. Recognition of pathogens by TLR receptors activate the NF-κB transcription factor, and lead to production of wide spectrum of cytokines (TNF-α, IL-1β, IL-6 and IL-8). Released by epithelium proinflammatory cytokines intensify migration of macrophages to damaged tissues and modulate their pro-inflammatory functions. Based on traditional use of G. squarrosa aerial parts we hypothesized that successful treatment of cold-related diseases may arise from modulation of the pro-inflammatory functions of respiratory epithelium and human monocytes/macrophages. The biological activity of G. squarrosa extract and grindelic acid were compared with clarithromycin and budesonide used as positive controls.

Methods: The expression of surface receptors (TLR-4, IL-10) and expression of adhesive molecules (ICAM-1, VCAM-1, E-selectin) was analyzed with flow cytometry. The macrophage attachment to the epithelial cells was assessed fluorimetrically. The p65 NF-κB concentration and cytokine production was measured spectrophotometrically using enzyme-linked immunosorbent assay. Antibacterial activity was examined by the standard disc-diffusion method and serial dilution method according to CLSI guidelines.

Results:G. squarrosa extract and grindelic acid had no antimicrobial effect. However, we noticed significant modulation of pro-inflammatory functions of LPS-stimulated nasal and bronchial epithelium. G. squarrosa extract treatment resulted in decrease of TLR-4 expression and p65 NF-κB concentration and inhibition of cytokines synthesis (IL-8, TNF-α, IL-1β and IL-6) in both cellular models. Additionally, G. squarrosa extract slightly modulated ICAM-1 expression affecting on attachment of macrophages to epithelium. Only G. squarrosa extract was able to stimulate the anti-inflammatory functions of macrophages by inducing TGF-β release and IL-10 receptor surface expression. Grindelic acid, identified as a dominant compound in the plant extract, modulated pro-inflammatory functions of epithelium and macrophages slightly.

Conclusion: The obtained results support traditional use of Grindelia squarrosa preparations for a treatment cold-associated diseases symptoms. In our opinion, the observed biological effect of extract may be a consequence of synergistic effect of all compounds present in the extract.

• Grindelia squarrosa
• cold syndrome
• grindelic acid
• inflammation
• macrophages
• respiratory epithelium

Mesenchymal stem cells (MSCs) have drawn lots of attention as gold standard stem cells in fundamental and clinical researches during the last 20 years. Due to their tissue and vascular repair capacities, MSCs have been used to treat a variety of degenerative disorders. Moreover, MSCs are able to modulate immune cells’ functions, particularly T cells while inducing regulatory T cells (iTregs). MSCs are very sensitive to inflammatory signals. Their biological functions could remarkably vary after exposure to different pro-inflammatory cytokines, notably TNFα. In this article, we have explored the importance of TNFR2 expression in a series of MSCs’ biological and functional properties. Thus, MSCs from wild-type (WT) and TNFR2 knockout (TNFR2 KO) mice were isolated and underwent several ex vivo experiments to investigate the biological significance of TNFR2 molecule in MSC main functions. Hampering in TNFR2 signaling resulted in reduced MSC colony-forming units and proliferation rate and diminished the expression of all MSC characteristic markers such as stem cell antigen-1 (Sca1), CD90, CD105, CD44, and CD73. TNFR2 KO-MSCs produced more pro-inflammatory cytokines like TNFα, IFNγ, and IL-6 and less anti-inflammatory mediators such as IL-10, TGFβ, and NO and induced Tregs with less suppressive effect. Furthermore, the TNFR2 blockade remarkably decreased MSC regenerative functions such as wound healing, complex tube formation, and endothelial pro-angiogenic support. Therefore, our results reveal the TNFα–TNFR2 axis as a crucial regulator of MSC immunological and regenerative functions.

• TNFα–TNFR2 signaling pathway
• angiogenesis
• immune-checkpoint
• immunoregulation
• mesenchymal stem cells
• tissue regeneration

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory capacity; therefore, they have been used in different clinical protocols in which it is necessary to decrease the immune response. This capacity is mainly regulated by TNF-α and IFN-γ, and it has been observed that cell-cell contact, mainly mediated by ICAM-1, is important for MSCs to carry out efficient immunoregulation. Therefore, in the present work, we analyzed the effect of TNF-α alone or in combination with IFN-γ on the expression of ICAM-1. Besides, given the importance of cell contact in the immunoregulatory function of MSCs, we analyzed whether these cells release ICAM-1⁺ microvesicles (MVs). Our results show for the first time that TNF-α is capable of increasing the early expression of ICAM-1 in human BM-MSCs. Also, we observed that TNF-α and IFN-γ have a synergistic effect on the increase in the expression of ICAM-1. Furthermore, we found that BM-MSCs exposed to an inflammatory environment release MVs enriched in ICAM-1 (MVs-ICAM-1^high). The knowledge generated in this study will contribute to the improvement of in vitro conditioning protocols that favor the therapeutic effect of these cells or their products.

• Base excision repair
• Homologous recombination
• Malignancy
• Mismatch repair
• Non-homologous end joining
• Nucleotide excision repair

• D-galactose
• MSCs
• aging SD rat model

• tissue engineering
• stem cells

• Animals
• Cell Line
• Female
• Humans
• Nucleic Acids/pharmacology
• Proto-Oncogene Proteins c-akt/metabolism
• Rats
• Rats, Sprague-Dawley
• Signal Transduction/drug effects
• Skin/injuries
• Skin/metabolism
• Wound Healing/drug effects
• Wounds and Injuries/drug therapy
• Wounds and Injuries/metabolism

• National Natural Science Foundation of China (National Science Foundation of China)

• Fungal keratitis
• adjuvant therapy
• corneal collagen crosslinking
• cytokines
• toll – like receptors