Abstract 120: Developing a novel intra-portal stem cell hydrogel carrier system for enhancing liver remnant hypertrophy and improving surgical eligibility for hepatocellular carcinoma: preclinical assessment in a murine model of portal vein blockade

Abstract Purpose: Hepatocellular carcinoma (HCC) is definitively treated with surgical resection of the affected lobe. However, 32% of patients are ineligible due to insufficient future liver remnant, which increases the risk of post-hepatectomy liver failure. To address this, portal vein blockade with mesenchymal stem cell (MSC) augmentation is used to induce pre-operative liver hypertrophy. However, 20-30% of patients fail to achieve adequate growth due to the rapid washout of MSCs from the liver. Therefore, we pioneered the use of hydrogels as stem cell carrier systems to enhance the retention, survival, and efficacy of MSCs in the liver to maximize hypertrophy. Materials and Methods: MSCs were loaded in 1.5% sodium alginate solution and cross-linked with CaCl2 to form hydrogels. The biocompatibility of the hydrogels and the release of MSCs were evaluated for 2 weeks. For in vivo modeling, portal vein blockade was achieved via left portal vein ligation (PVL) in cirrhotic Sprague-Dawley rats, effectively cutting off circulation into the ipsilateral lobe. The treatment groups (n≥4) are untreated control, PVL (surgery only), PVL+MSC (surgery with intraportal 1x 106 MSCs injection), and PVL+MSC+hydrogel (surgery with intraportal injection of hydrogel carrier system loaded with 1 x 106 MSCs). The treatment effect was monitored using CT volumetry and liver tests. After two weeks, the animals were sacrificed and livers were collected for liver growth calculation, collagen staining, and MSC immunostaining. Statistical significance is defined as p<0.05. Results: The hydrogel carrier system showed excellent biocompatibility by maintaining high MSC viability (89.0 ± 3.0 %) for 2 weeks. The system demonstrated an initial burst release over 7 days (64.6 ± 4.5%) followed by a more gradual release up to 2 weeks (87.0 ± 2.0%), which is ideal for the controlled delivery of therapeutic MSCs. On CT volumetry, PVL+MSC+hydrogel showed the highest liver growth among the treatment groups at 79.61% from baseline. Furthermore, PVL+MSC+hydrogel improved serum liver markers, such as AST, ALP, and ALT, compared to the PVL and PVL+MSC. On collagen staining, PVL+MSC+hydrogel revealed the highest reduction in fibrosis at 27.4%. Lastly, MSC retention with the alginate hydrogel carrier system in the liver remnant was 41.8% higher than PVL+MSC. Conclusion: We successfully developed a stem cell hydrogel carrier system with ideal physicochemical and biological properties. The cell-loaded carrier system allowed the improvement of the structure and function of the liver. This is crucial for sustaining therapeutic and regenerative effects of MSCs for liver hypertrophy. Adapting this technology will enhance future liver remnant growth and thus, improve survivability among patients with HCC. Citation Format: Dominic Karl M. Bolinas, Allan John R. Barcena, Archana Mishra, Marvin R. Bernardino, Steven Y. Huang, Marites P. Melancon. Developing a novel intra-portal stem cell hydrogel carrier system for enhancing liver remnant hypertrophy and improving surgical eligibility for hepatocellular carcinoma: preclinical assessment in a murine model of portal vein blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 120.