Stem Cell-Based Treatment Is Promising for Prolonging the Survival of Patients with Liver Failure
This paper assesses how adipose-derived mesenchymal stem cells can be used in the treatment of liver failure.
ABSTRACT
Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity.
Stem Cell Res Ther. 2019 Oct 16;10(1):230. doi: 10.1186/s13287-019-1337-3.
Regmi S1, Pathak S1, Thanh TP1, Nguyen TT1, Sung JH2, Yook S3, Kim JO1, Yong CS1, Choi I4, Doh KO5, Park PH1, Park JB6, Seo Y7,8, Kim BK5, Lee DM9, Moon IJ10, Kim HS11,12, Jeong JH13.
Author information
- College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan-si, Gyeongbuk-do, 38541, Republic of Korea.
- College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.
- College of Pharmacy, Keimyung University, Daegu, 42415, Republic of Korea.
- Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
- Department of Physiology, College of Medicine, Yeungnam University, Daegu, 42415, Republic of Korea.
- Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea.
- Institute for Translational Dental Sciences, Pusan National University, Yangsan, 50612, Republic of Korea.
- Biomedical Manufacturing Technology Center, Korea Institute of Industrial Technology, Gyeongbuk, 38822, Republic of Korea.
- WELGENE Inc., Gyeongsan, 38695, Republic of Korea.
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea. [email protected].
- Institute for Translational Dental Sciences, Pusan National University, Yangsan, 50612, Republic of Korea. [email protected].
- College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan-si, Gyeongbuk-do, 38541, Republic of Korea. [email protected].
BACKGROUND:
Systemic inflammatory response syndrome (SIRS) is common in severe fulminant hepatic failure (FHF) and has a high mortality rate (20-50%) due to irreversible cerebral edema or sepsis. Stem cell-based treatment has emerged as a promising alternative therapeutic strategy to prolong the survival of patients suffering from FHF via the inhibition of SIRS due to their immunomodulatory effects.
METHODS:
3D spheroids of adipose-derived mesenchymal stem cells (3D-ADSC) were prepared by the hanging drop method. The efficacy of the 3D-ADSC to rescue FHF was evaluated in a D-galactosamine/lipopolysaccharide (GalN/LPS)-induced mouse model of FHF via intraportal transplantation of the spheroids.
RESULTS:
Intraportally delivered 3D-ADSC better engrafted and localized into the damaged livers compared to 2D-cultured adipose-derived mesenchymal stem cells (2D-ADSC). Transplantation of 3D-ADSC rescued 50% of mice from FHF-induced lethality, whereas only 20% of mice survived when 2D-ADSC were transplanted. The improved transplantation outcomes correlated with the enhanced immunomodulatory effect of 3D-ADSC in the liver microenvironment.
CONCLUSIONS:
The study shows that the transplantation of optimized 3D-ADSC can efficiently ameliorate GalN/LPS-induced FHF due to improved viability, resistance to exogenous ROS, and enhanced immunomodulatory effects of 3D-ADSC.
PMID:31615539
DOI:10.1186/s13287-019-1337-3