Mohan Prasoon P, Deo Sapna, Liu Zhao-Jun, Dikici Emre, Kaneku Hugo, Chang Doyoung, Garcia-Buitrago Monica, Jalaeian Hamed, Zeynaloo Elnaz, Ortiz Yulexi Y, Li Yan, Bhatia Shivank, Velazquez Omaida, Daunert Sylvia
Department of Interventional Radiology, University of Miami Miller School of Medicine, Miami, FL, USA.
Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA.
Cardiovasc Intervent Radiol. 2025 Feb;48(2):233-243. doi: 10.1007/s00270-024-03862-2. Epub 2024 Nov 6.
To test the efficacy of nanocarrier (NC) mediated mesenchymal stem cell (MSC) therapy for liver regeneration following thermal ablation of porcine livers.
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.
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).
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.
测试纳米载体（NC）介导的间充质干细胞（MSC）疗法对猪肝脏热消融后肝脏再生的疗效。
对18头猪进行肝脏射频消融，分为MSC组、MSC+NC组和对照组。测试组通过肝动脉输注用增强型绿色荧光蛋白（eGFP）标记的MSC或MSC+NC。MSC+NC组的MSC用与淋巴细胞功能相关抗原-1（LFA-1）的I结构域复合的树枝状聚合物纳米载体包被。纳米载体通过与细胞间粘附分子-1（ICAM-1）结合来引导MSC归巢，ICAM-1在炎症引起的消融边缘周围过度表达。通过CT容积测量法测量消融腔缩小情况，以此作为肝脏再生的替代指标。用Ki67和HepPar-1染色评估细胞增殖。通过GFP鉴定MSC衍生细胞。
对照组4只动物共进行了13次消融。MSC组6只动物进行了23次消融，MSC+NC组6只动物进行了21次消融。从第0天到第30天，对照组、MSC组和MSC+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%（MSC+NC组与MSC组比较：p<0.001，MSC+NC组与对照组比较：p=0.001）。MSC组边缘的GFP细胞计数为426.8±193.2，MSC+NC组为498.6±235.2（p=0.01）。MSC+NC组边缘的平均Ki67和HepPar-1染色分别为9.81±4.5%和6.12±4.2%，而MSC组分别为7.59±3.7%和5.09±3.7%（分别为P<0.001和P=0.09）。
纳米载体介导的MSC疗法通过将MSC植入消融边缘促进肝脏再生，这可能使针对严重肝功能不全患者的肝脏定向治疗成为可行方案。该技术可能对其他实体器官也有益处。
