Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats.

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.