Bolinas Dominic Karl M, Barcena Allan John R, Mishra Archana, Bernardino Marvin R, Lin Vincent, Heralde Francisco M, Chintalapani Gouthami, Fowlkes Natalie W, Huang Steven Y, Melancon Marites P
Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
College of Medicine, University of the Philippines Manila, Manila 1000, Philippines.
Gels. 2025 Mar 27;11(4):250. doi: 10.3390/gels11040250.
Cirrhosis, a marker of severe liver diseases, limits future liver remnant (FLR) growth, preventing many cancer patients from undergoing surgery. While portal vein blockade (PVB) techniques are used to stimulate liver regeneration, 20-30% of patients still fail to achieve the required growth. Although mesenchymal stem cell (MSC) therapy improves PVB, its efficacy is limited by poor cell retention. To address this, we utilized alginate hydrogels to deliver MSCs and improve their retention. MSCs were loaded in the hydrogel and injected intraportally in cirrhotic rats. Liver volume, weights, enzyme levels, and histology were monitored. Results showed that the hydrogel maintained 89.0 ± 3.0% cell viability and gradually released MSCs for over two weeks. Furthermore, the rats injected with the MSC-loaded hydrogel demonstrated higher liver volumes (FLR ratio of 0.57 ± 0.32) and weights (FLR ratio of 0.84 ± 0.05). The treated rats exhibited more improved liver enzymes (AST: 72.75 ± 14.17 U/L, ALP: 135.67 ± 41.20 U/L, ALT: 46.00 ± 2.94 U/L) and decreased fibrotic areas in the liver (4.52 ± 0.22%) compared to the control group. Histology revealed increased retention when MSCs were delivered with the hydrogel (37.30 ± 16.10 MSCs/mm) compared to cells alone (21.70 ± 22.10 MSCs/mm). Overall, the MSC-loaded hydrogels enhanced the growth and reduced the fibrosis of the liver by promoting cell retention and efficacy in cirrhotic rats. This approach holds significant potential for improving outcomes among cancer patients, offering a promising therapeutic strategy for liver regeneration and treatment of liver diseases.
肝硬化是严重肝脏疾病的一个标志，它会限制未来肝剩余量（FLR）的增长，使许多癌症患者无法接受手术。虽然门静脉阻断（PVB）技术用于刺激肝脏再生，但仍有20%至30%的患者未能实现所需的肝脏增长。尽管间充质干细胞（MSC）疗法可改善PVB，但其疗效因细胞留存不佳而受限。为解决这一问题，我们利用藻酸盐水凝胶来递送MSC并提高其留存率。将MSC加载到水凝胶中并经门静脉注射到肝硬化大鼠体内。监测肝脏体积、重量、酶水平和组织学情况。结果显示，水凝胶保持了89.0±3.0%的细胞活力，并在两周多的时间里逐渐释放MSC。此外，注射了加载MSC水凝胶的大鼠肝脏体积（FLR比率为0.57±0.32）和重量（FLR比率为0.84±0.05）更高。与对照组相比，接受治疗的大鼠肝脏酶水平有更大改善（AST：72.75±14.17 U/L，ALP：135.67±41.20 U/L，ALT：46.00±2.94 U/L），且肝脏纤维化区域减少（4.52±0.22%）。组织学检查显示，与单独注射细胞（21.70±22.10个MSC/mm）相比，当MSC与水凝胶一起递送时留存率增加（37.30±16.10个MSC/mm）。总体而言，加载MSC的水凝胶通过促进细胞留存和提高疗效，增强了肝硬化大鼠肝脏的生长并减少了纤维化。这种方法在改善癌症患者预后方面具有巨大潜力，为肝脏再生和肝脏疾病治疗提供了一种有前景的治疗策略。
