Prasoon P Mohan, Sapna Deo, Zhao-Jun Liu, Emre Dikici, Hugo Kaneku, Doyoung Chang, Monica Garcia-Buitrago, Hamed Jalaeian, Elnaz Zeynaloo, Yulexi Y Ortiz, Yan Li, Shivank Bhatia, Omaida Velazquez, Sylvia Daunert
{"title":"Liver Regeneration Following Thermal Ablation Using Nanocarrier Mediated Targeted Mesenchymal Stem Cell Therapy.","authors":"Prasoon P Mohan, Sapna Deo, Zhao-Jun Liu, Emre Dikici, Hugo Kaneku, Doyoung Chang, Monica Garcia-Buitrago, Hamed Jalaeian, Elnaz Zeynaloo, Yulexi Y Ortiz, Yan Li, Shivank Bhatia, Omaida Velazquez, Sylvia Daunert","doi":"10.1007/s00270-024-03862-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To test the efficacy of nanocarrier (NC) mediated mesenchymal stem cell (MSC) therapy for liver regeneration following thermal ablation of porcine livers.</p><p><strong>Materials and methods: </strong>Liver radiofrequency ablation was performed in 18 swines divided into MSC, MSC + NC and control groups. The test groups received infusion of MSC or MSC + NC labeled with enhanced green fluorescent protein (eGFP) via hepatic artery. MSC + NC group had MSCs coated with dendrimer nanocarrier complexed with I-Domain of lymphocyte function-associated antigen-1 (LFA-1). Nanocarriers direct homing of MSCs by binding to its counterpart protein, intercellular adhesion molecule-1 (ICAM-1), which is overexpressed at the periablation margins from inflammation. Ablation cavity reduction by CT volumetry was used as surrogate marker for liver regeneration. Cell proliferation was assessed with Ki67 and HepPar-1 stains. GFP identified MSC derived cells.</p><p><strong>Results: </strong>Total number of ablations in control animals were 13 across 4 animals. In the MSC group, there were 23 ablations across 6 animals, and in MSC + NC group there were 21 ablations across 6 animals. Ablation cavity volume reduction from day 0 to 30 were 64.4 ± 15.0%, 61.5 ± 12.9% and 80.3 ± 9.4% for control, MSC and MSC + NC groups, respectively (MSC + NC vs MSC: p < 0.001, MSC + NC vs. control: p = 0.001). GFP<sup>+</sup> cell count at margins was 426.8 ± 193.2 for MSC group and 498.6 ± 235.2 for MSC + NC group (p = 0.01). The mean Ki67 and HepPar-1 staining at margins were 9.81 ± 4.5% and 6.12 ± 4.2% for MSC + NC group versus 7.59 ± 3.7% and 5.09 ± 3.7% for MSC group, respectively (P < 0.001 and P = 0.09, respectively).</p><p><strong>Conclusion: </strong>Nanocarrier-mediated MSC therapy promotes liver regeneration by engrafting MSCs at ablation margins, potentially making liver-directed therapy viable for patients with severe liver dysfunction. This technology may also benefit other solid organs.</p>","PeriodicalId":9591,"journal":{"name":"CardioVascular and Interventional Radiology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CardioVascular and Interventional Radiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00270-024-03862-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: To test the efficacy of nanocarrier (NC) mediated mesenchymal stem cell (MSC) therapy for liver regeneration following thermal ablation of porcine livers.
Materials and methods: Liver radiofrequency ablation was performed in 18 swines divided into MSC, MSC + NC and control groups. The test groups received infusion of MSC or MSC + NC labeled with enhanced green fluorescent protein (eGFP) via hepatic artery. MSC + NC group had MSCs coated with dendrimer nanocarrier complexed with I-Domain of lymphocyte function-associated antigen-1 (LFA-1). Nanocarriers direct homing of MSCs by binding to its counterpart protein, intercellular adhesion molecule-1 (ICAM-1), which is overexpressed at the periablation margins from inflammation. Ablation cavity reduction by CT volumetry was used as surrogate marker for liver regeneration. Cell proliferation was assessed with Ki67 and HepPar-1 stains. GFP identified MSC derived cells.
Results: Total number of ablations in control animals were 13 across 4 animals. In the MSC group, there were 23 ablations across 6 animals, and in MSC + NC group there were 21 ablations across 6 animals. Ablation cavity volume reduction from day 0 to 30 were 64.4 ± 15.0%, 61.5 ± 12.9% and 80.3 ± 9.4% for control, MSC and MSC + NC groups, respectively (MSC + NC vs MSC: p < 0.001, MSC + NC vs. control: p = 0.001). GFP+ cell count at margins was 426.8 ± 193.2 for MSC group and 498.6 ± 235.2 for MSC + NC group (p = 0.01). The mean Ki67 and HepPar-1 staining at margins were 9.81 ± 4.5% and 6.12 ± 4.2% for MSC + NC group versus 7.59 ± 3.7% and 5.09 ± 3.7% for MSC group, respectively (P < 0.001 and P = 0.09, respectively).
Conclusion: Nanocarrier-mediated MSC therapy promotes liver regeneration by engrafting MSCs at ablation margins, potentially making liver-directed therapy viable for patients with severe liver dysfunction. This technology may also benefit other solid organs.
期刊介绍:
CardioVascular and Interventional Radiology (CVIR) is the official journal of the Cardiovascular and Interventional Radiological Society of Europe, and is also the official organ of a number of additional distinguished national and international interventional radiological societies. CVIR publishes double blinded peer-reviewed original research work including clinical and laboratory investigations, technical notes, case reports, works in progress, and letters to the editor, as well as review articles, pictorial essays, editorials, and special invited submissions in the field of vascular and interventional radiology. Beside the communication of the latest research results in this field, it is also the aim of CVIR to support continuous medical education. Articles that are accepted for publication are done so with the understanding that they, or their substantive contents, have not been and will not be submitted to any other publication.