Wanting Xu, Xiaolin Jieda, Yue Wu, Fengling Du, Lu Ma, Lijuan Luo, Dong Liu, Ling Guo, Jing Liu, Wenbin Dong
{"title":"人脐带间充质干细胞外泌体鼻内给药治疗支气管肺发育不良小鼠模型的安全性、有效性和生物分布分析","authors":"Wanting Xu, Xiaolin Jieda, Yue Wu, Fengling Du, Lu Ma, Lijuan Luo, Dong Liu, Ling Guo, Jing Liu, Wenbin Dong","doi":"10.2147/IJN.S501843","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) hold great potential for treating bronchopulmonary dysplasia (BPD); however, safety concerns and effects of intranasal administration remain unexplored. This study aimed to explore the safety of hUC-MSCs and Exos and to investigate the efficacy and bio-distribution of repeated intranasal Exos administration in neonatal BPD models.</p><p><strong>Methods: </strong>Characteristics of hUC-MSCs and Exos were analyzed. A subcutaneous tumor formation assay using a single dose of hUC-MSCs or Exos was conducted in Crl:NU-Foxn1nu mice. Vital signs, biochemical indices, pathological alterations, and <sup>18</sup>F-FDG microPET/CT analysis were examined. Pulmonary pathology, three-dimensional reconstructions, ultrastructural structures, in vivo and ex vivo bio-distribution imaging analyses, enzyme-linked immunoassay assays, and reverse transcription-quantitative polymerase chain reaction analyses of lung tissues were all documented following intranasal Exos administration.</p><p><strong>Results: </strong>Characteristics of hUC-MSCs and Exos satisfied specifications. Crl:NU-Foxn1nu mice did not exhibit overt toxicity or carcinogenicity following a single dose of hUC-MSCs or Exos after 60 days of observation. Repeated intranasal Exos administration effectively alleviated pathological injuries, restored pulmonary ventilation in three-dimensional reconstruction, and recovered endothelial cell layer integrity in ultrastructural analysis. Exos steadily accumulated in lung tissues from postnatal day 1 to 14. Exos also interrupted the epithelial-mesenchymal transition and inflammation reactions in BPD models.</p><p><strong>Conclusion: </strong>As a nanoscale, non-cellular therapy, intranasal administration of Exos was an effective, noninvasive treatment for BPD. This approach was free from toxic, tumorigenic risks and repaired alveolar damage while interrupting epithelial-mesenchymal transition and inflammation in neonatal mice with BPD.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"2521-2553"},"PeriodicalIF":6.6000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874997/pdf/","citationCount":"0","resultStr":"{\"title\":\"Safety, Efficacy and Bio-Distribution Analysis of Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells for Effective Treatment of Bronchopulmonary Dysplasia by Intranasal Administration in Mice Model.\",\"authors\":\"Wanting Xu, Xiaolin Jieda, Yue Wu, Fengling Du, Lu Ma, Lijuan Luo, Dong Liu, Ling Guo, Jing Liu, Wenbin Dong\",\"doi\":\"10.2147/IJN.S501843\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) hold great potential for treating bronchopulmonary dysplasia (BPD); however, safety concerns and effects of intranasal administration remain unexplored. This study aimed to explore the safety of hUC-MSCs and Exos and to investigate the efficacy and bio-distribution of repeated intranasal Exos administration in neonatal BPD models.</p><p><strong>Methods: </strong>Characteristics of hUC-MSCs and Exos were analyzed. A subcutaneous tumor formation assay using a single dose of hUC-MSCs or Exos was conducted in Crl:NU-Foxn1nu mice. Vital signs, biochemical indices, pathological alterations, and <sup>18</sup>F-FDG microPET/CT analysis were examined. Pulmonary pathology, three-dimensional reconstructions, ultrastructural structures, in vivo and ex vivo bio-distribution imaging analyses, enzyme-linked immunoassay assays, and reverse transcription-quantitative polymerase chain reaction analyses of lung tissues were all documented following intranasal Exos administration.</p><p><strong>Results: </strong>Characteristics of hUC-MSCs and Exos satisfied specifications. Crl:NU-Foxn1nu mice did not exhibit overt toxicity or carcinogenicity following a single dose of hUC-MSCs or Exos after 60 days of observation. Repeated intranasal Exos administration effectively alleviated pathological injuries, restored pulmonary ventilation in three-dimensional reconstruction, and recovered endothelial cell layer integrity in ultrastructural analysis. Exos steadily accumulated in lung tissues from postnatal day 1 to 14. Exos also interrupted the epithelial-mesenchymal transition and inflammation reactions in BPD models.</p><p><strong>Conclusion: </strong>As a nanoscale, non-cellular therapy, intranasal administration of Exos was an effective, noninvasive treatment for BPD. This approach was free from toxic, tumorigenic risks and repaired alveolar damage while interrupting epithelial-mesenchymal transition and inflammation in neonatal mice with BPD.</p>\",\"PeriodicalId\":14084,\"journal\":{\"name\":\"International Journal of Nanomedicine\",\"volume\":\"20 \",\"pages\":\"2521-2553\"},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2025-02-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874997/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Nanomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/IJN.S501843\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"NANOSCIENCE & NANOTECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Nanomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJN.S501843","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
Safety, Efficacy and Bio-Distribution Analysis of Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells for Effective Treatment of Bronchopulmonary Dysplasia by Intranasal Administration in Mice Model.
Purpose: Exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) hold great potential for treating bronchopulmonary dysplasia (BPD); however, safety concerns and effects of intranasal administration remain unexplored. This study aimed to explore the safety of hUC-MSCs and Exos and to investigate the efficacy and bio-distribution of repeated intranasal Exos administration in neonatal BPD models.
Methods: Characteristics of hUC-MSCs and Exos were analyzed. A subcutaneous tumor formation assay using a single dose of hUC-MSCs or Exos was conducted in Crl:NU-Foxn1nu mice. Vital signs, biochemical indices, pathological alterations, and 18F-FDG microPET/CT analysis were examined. Pulmonary pathology, three-dimensional reconstructions, ultrastructural structures, in vivo and ex vivo bio-distribution imaging analyses, enzyme-linked immunoassay assays, and reverse transcription-quantitative polymerase chain reaction analyses of lung tissues were all documented following intranasal Exos administration.
Results: Characteristics of hUC-MSCs and Exos satisfied specifications. Crl:NU-Foxn1nu mice did not exhibit overt toxicity or carcinogenicity following a single dose of hUC-MSCs or Exos after 60 days of observation. Repeated intranasal Exos administration effectively alleviated pathological injuries, restored pulmonary ventilation in three-dimensional reconstruction, and recovered endothelial cell layer integrity in ultrastructural analysis. Exos steadily accumulated in lung tissues from postnatal day 1 to 14. Exos also interrupted the epithelial-mesenchymal transition and inflammation reactions in BPD models.
Conclusion: As a nanoscale, non-cellular therapy, intranasal administration of Exos was an effective, noninvasive treatment for BPD. This approach was free from toxic, tumorigenic risks and repaired alveolar damage while interrupting epithelial-mesenchymal transition and inflammation in neonatal mice with BPD.
期刊介绍：
The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area.
With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field.
Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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