Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Lung Injury in Rat Model of Bronchopulmonary Dysplasia by Affecting Cell Survival and Angiogenesis

You, Jingyi; Ou, Zhou; Liu, Jiang; Zou, Wenjing; Zhang, Linghuan; Tian, Daiyin; Dai, Jihong; Luo, Zhengxiu; Liu, Enmei; Fu, Zhou; Zou, Lin

doi:10.1089/scd.2020.0156

Cited by 44 publications

(42 citation statements)

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“…Although there is not yet effective treatment for BPD, the advent of MSCs provides new hope for BPD treatment. Previous studies have demonstrated that small extracellular vesicles (or exosomes) mediate the therapeutic effects of MSCs on BPD [18,21,30]. However, the therapeutic effects and function of large extracellular vesicles (or MVs) derived from MSCs on BPD are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…One 4-mm-thick transverse section was taken from the midplane of the left lobe of the xed lungs per animal and processed and embedded in para n wax. All the sections were stained with hematoxylin and eosin, and alveolarization was assessed by performing RAC, secondary septa count, and MLI as previously described 18 .…”

Section: Lung Alveolarization Assessmentmentioning

confidence: 99%

“…Human umbilical cord mesenchymal stem cells (hUCMSCs), with low immunogenicity and easy accessibility, are effective for in ammatory disease treatment and regenerative medicine [16]. Our group has previously revealed the bene cial effect of hUCMSCs on alleviating BPD in an animal model of exposure to postnatal hyperoxia [17,18]. However, there have been no studies regarding the treatment effect of mesenchymal stem cells (MSCs) on BPD induced by antenatal factors.…”

Section: Introductionmentioning

confidence: 99%

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Microvesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Development and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia Induced by Antenatal Lipopolysaccharide

Ou¹,

You²,

Xu³

et al. 2021

Preprint

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BackgroundAlthough it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide (LPS)-induced BPD rat model and to clarify the underlying mechanism.MethodsPregnant rats received intra-amniotic injections of LPS on day 20.5 of gestation (term=day 22.5 of gestion), and pups were delivered by cesarean section on embryonic day 22.5 (E22.5). MVs were isolated by ultracentrifugation and then were characterized. hUCMSCs and MVs were administered intratracheally on postnatal day 7 (PN7). On PN14, lung function was measured, and tissues were harvested to determine alveolarization. Immunofluorescence staining was used to determine the co-localization of MVs and lung cells. Cell proliferation was measured by Ki-67 staining, and apoptosis was determined by flow cytometry using 7-ADD and Annexin V. The expression levels of AKT, p38, JNK, ERK, and their phosphorylated forms, PTEN and VEGF, were measured by WB.ResultsAntenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature. Both hUCMSCs and MVs successfully promoted alveolar development and improved lung function. However, hUCMSCs but not MVs restored the loss of pulmonary microvascular vessels (<100 μm). Furthermore, MVs were mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, upregulated expression of p-AKT, downregulated expression of PTEN, as well as inhibition of MAPK pathway were observed in MVs-treated BPD rats.ConclusionsMVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuate lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Lung Alveolarization Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microvesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Development and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia Induced by Antenatal Lipopolysaccharide

Ou¹,

You²,

Xu³

et al. 2021

Preprint

Self Cite

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“…Human umbilical cord mesenchymal stem cells (hUC-MSCs) are isolated from umbilical Wharton's Jelly, capable of differentiating into three germ layers [22]. In addition, hUC-MSCs have been proven to exert therapeutic effects in some kinds of diseases, including the kidney, liver, and lung [23][24][25][26]. For pulmonary diseases, acute respiratory distress syndrome and bronchopulmonary dysplasia were the examples [25,26].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, hUC-MSCs have been proven to exert therapeutic effects in some kinds of diseases, including the kidney, liver, and lung [23][24][25][26]. For pulmonary diseases, acute respiratory distress syndrome and bronchopulmonary dysplasia were the examples [25,26]. Moreover, hUC-MSCs can differentiate into neurons, astrocytes, hepatocytes, and islet cells [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Type 2 Alveolar Epithelial Cells Differentiated from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Mouse Pulmonary Fibrosis Through β-Catenin-Regulated Cell Apoptosis

Liu

Peng

You

et al. 2021

Stem Cells and Development

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Pulmonary fibrosis (PF) is a chronic, progressive, and lethal disease with little response to available therapies. One of the major mechanisms of PF is the repeated injury and inadequate regeneration of the alveolar epithelium. In this study, we induced human umbilical cord mesenchymal stem cells (hUC-MSCs) to differentiate into type 2 alveolar epithelial cells (AEC2s), and we provided evidence that intratracheal transplantation of hUC-MSC-derived AEC2s (MSC-AEC2s) could improve mortality and alleviate fibrosis in bleomycin-induced PF mice. Transplantation of MSC-AEC2s could increase the AEC2 cell count in these mice, and the results of the cell tracing experiment exhibited that the increased AEC2s originated from the self-renewal of mouse alveolar epithelium. The AEC2 survival was controlled by the apoptosis of AEC2s via the expression of bcatenin in PF mice. In in vitro experiments, MSC-AEC2s could alleviate the apoptosis of MLE-12 cells induced by transforming growth factor beta (TGF-b1), which could be eliminated by using PRI-724, a b-catenin inhibitor, suggesting b-catenin signaling involved in the protection against apoptosis provided by MSC-AEC2s. Our study demonstrated that MSC-AEC2s could protect PF mice through regulating apoptosis mediated by bcatenin, which provided a viable strategy for the treatment of PF.

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The effect of bioactivity of airway epithelial cells using methacrylated gelatin scaffold loaded with exosomes derived from bone marrow mesenchymal stem cells

Li,

Chen,

Xia

et al. 2024

J Biomedical Materials Res

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The current evidence provides support for the involvement of bone marrow mesenchymal stem cells (BMSCs) in the regulation of airway epithelial cells. However, a comprehensive understanding of the underlying biological mechanisms remains elusive. This study aimed to isolate and characterize BMSC‐derived exosomes (BMSC‐Exos) and epithelial cells (ECs) through primary culture. Subsequently, the impact of BMSC‐Exos on ECs was assessed in vitro, and sequencing analysis was conducted to identify potential molecular mechanisms involved in these interactions. Finally, the efficacy of BMSC‐Exos was evaluated in animal models in vivo. In this study, primary BMSCs and ECs were efficiently isolated and cultured, and high‐purity Exos were obtained. Upon uptake of BMSC‐Exos, ECs exhibited enhanced proliferation (p < .05), while migration showed no difference (p > .05). Notably, invasion demonstrated significant difference (p < .05). Sequencing analysis suggested that miR‐21‐5p may be the key molecule responsible for the effects of BMSC‐Exos, potentially mediated through the MAPK or PI3k‐Akt signaling pathway. The in vivo experiments showed that the presence of methacrylated gelatin (GelMA) loaded with BMSC‐Exos in composite scaffold significantly enhanced epithelial crawling in the patches in comparison to the pure decellularized group. In conclusion, this scheme provides a solid theoretical foundation and novel insights for the research and clinical application of tracheal replacement in the field of tissue engineering.

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Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Lung Injury in Rat Model of Bronchopulmonary Dysplasia by Affecting Cell Survival and Angiogenesis

Cited by 44 publications

References 44 publications

Microvesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Development and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia Induced by Antenatal Lipopolysaccharide

Microvesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Development and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia Induced by Antenatal Lipopolysaccharide

Type 2 Alveolar Epithelial Cells Differentiated from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Mouse Pulmonary Fibrosis Through β-Catenin-Regulated Cell Apoptosis

The effect of bioactivity of airway epithelial cells using methacrylated gelatin scaffold loaded with exosomes derived from bone marrow mesenchymal stem cells

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