{"title":"Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA.","authors":"Azar Abbas, Xiaosheng Huang, Aftab Ullah, Lishi Luo, Wenqun Xi, Yuanjiao Qiao, Kun Zeng","doi":"10.1186/s10020-024-00940-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>A spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study.</p><p><strong>Objective: </strong>This study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI).</p><p><strong>Methods: </strong>iPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining.</p><p><strong>Results: </strong>The results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration.</p><p><strong>Conclusion: </strong>These results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"168"},"PeriodicalIF":6.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446086/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10020-024-00940-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: A spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study.
Objective: This study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI).
Methods: iPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining.
Results: The results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration.
Conclusion: These results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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