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. Althoug...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Gels |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2310-2861/11/4/250 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850144101213667328 |
|---|---|
| author | Dominic Karl M. Bolinas Allan John R. Barcena Archana Mishra Marvin R. Bernardino Vincent Lin Francisco M. Heralde Gouthami Chintalapani Natalie W. Fowlkes Steven Y. Huang Marites P. Melancon |
| author_facet | Dominic Karl M. Bolinas Allan John R. Barcena Archana Mishra Marvin R. Bernardino Vincent Lin Francisco M. Heralde Gouthami Chintalapani Natalie W. Fowlkes Steven Y. Huang Marites P. Melancon |
| author_sort | Dominic Karl M. Bolinas |
| collection | DOAJ |
| description | 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<sup>2</sup>) compared to cells alone (21.70 ± 22.10 MSCs/mm<sup>2</sup>). 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. |
| format | Article |
| id | doaj-art-ecc03e8622a34151bbfe26fcf350c61c |
| institution | OA Journals |
| issn | 2310-2861 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj-art-ecc03e8622a34151bbfe26fcf350c61c2025-08-20T02:28:28ZengMDPI AGGels2310-28612025-03-0111425010.3390/gels11040250Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic RatsDominic Karl M. Bolinas0Allan John R. Barcena1Archana Mishra2Marvin R. Bernardino3Vincent Lin4Francisco M. Heralde5Gouthami Chintalapani6Natalie W. Fowlkes7Steven Y. Huang8Marites P. Melancon9Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USACollege of Medicine, University of the Philippines Manila, Manila 1000, PhilippinesDepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USACirrhosis, 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<sup>2</sup>) compared to cells alone (21.70 ± 22.10 MSCs/mm<sup>2</sup>). 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.https://www.mdpi.com/2310-2861/11/4/250alginatehydrogelmesenchymal stem cellsliver cirrhosis |
| spellingShingle | Dominic Karl M. Bolinas Allan John R. Barcena Archana Mishra Marvin R. Bernardino Vincent Lin Francisco M. Heralde Gouthami Chintalapani Natalie W. Fowlkes Steven Y. Huang Marites P. Melancon Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats Gels alginate hydrogel mesenchymal stem cells liver cirrhosis |
| title | Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats |
| title_full | Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats |
| title_fullStr | Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats |
| title_full_unstemmed | Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats |
| title_short | Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats |
| title_sort | mesenchymal stem cells loaded in injectable alginate hydrogels promote liver growth and attenuate liver fibrosis in cirrhotic rats |
| topic | alginate hydrogel mesenchymal stem cells liver cirrhosis |
| url | https://www.mdpi.com/2310-2861/11/4/250 |
| work_keys_str_mv | AT dominickarlmbolinas mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT allanjohnrbarcena mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT archanamishra mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT marvinrbernardino mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT vincentlin mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT franciscomheralde mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT gouthamichintalapani mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT nataliewfowlkes mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT stevenyhuang mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats AT maritespmelancon mesenchymalstemcellsloadedininjectablealginatehydrogelspromotelivergrowthandattenuateliverfibrosisincirrhoticrats |