Liver Regeneration Following Thermal Ablation Using Nanocarrier Mediated Targeted Mesenchymal Stem Cell Therapy.

IF 2.8 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS CardioVascular and Interventional Radiology Pub Date : 2024-11-06 DOI:10.1007/s00270-024-03862-2
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
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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.

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利用纳米载体介导的靶向间充质干细胞疗法实现热消融后的肝脏再生
目的:测试纳米载体(NC)介导的间充质干细胞(MSC)疗法对猪肝热消融后肝脏再生的疗效:对18头猪进行肝脏射频消融术,分为间充质干细胞组、间充质干细胞+NC组和对照组。试验组通过肝动脉输注标记有增强型绿色荧光蛋白(eGFP)的间充质干细胞或间充质干细胞+NC。间充质干细胞+NC组的间充质干细胞涂有与淋巴细胞功能相关抗原-1(LFA-1)I-域复合的树枝形分子纳米载体。纳米载体与间充质干细胞的对应蛋白细胞间粘附分子-1(ICAM-1)结合,从而引导间充质干细胞归巢。通过 CT 容积测量消融腔的缩小作为肝脏再生的替代指标。细胞增殖通过 Ki67 和 HepPar-1 染色法进行评估。GFP 可识别间充质干细胞:结果:对照组 4 只动物共消融了 13 个细胞。在间充质干细胞组中,6只动物共进行了23次消融;在间充质干细胞+NC组中,6只动物共进行了21次消融。从第 0 天到第 30 天,对照组、间充质干细胞组和间充质干细胞+NC 组的消融腔体积缩小率分别为 64.4 ± 15.0%、61.5 ± 12.9% 和 80.3 ± 9.4%(间充质干细胞+NC 组与间充质干细胞组相比:间充质干细胞组边缘细胞数为 426.8 ± 193.2,间充质干细胞+NC 组边缘细胞数为 498.6 ± 235.2(P = 0.01))。MSC + NC 组边缘的平均 Ki67 和 HepPar-1 染色率分别为 9.81 ± 4.5%和 6.12 ± 4.2%,而 MSC 组分别为 7.59 ± 3.7%和 5.09 ± 3.7%(P纳米载体介导的间充质干细胞疗法通过在消融边缘移植间充质干细胞促进肝脏再生,可能使严重肝功能障碍患者的肝脏定向疗法变得可行。这项技术还可能惠及其他实体器官。
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来源期刊
CiteScore
5.50
自引率
13.80%
发文量
306
审稿时长
3-8 weeks
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.
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