Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1337-3 |
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| author | Shobha Regmi Shiva Pathak Tung Pham Thanh Tiep Tien Nguyen Jong-Hyuk Sung Simmyung Yook Jong Oh. Kim Chul Soon Yong Inho Choi Kyoung-Oh Doh Pil-Hoon Park Jun-Beom Park Yoojin Seo Bieong-Kil Kim Dong-Mok Lee Ik-Jae Moon Hyung-Sik Kim Jee-Heon Jeong |
| author_facet | Shobha Regmi Shiva Pathak Tung Pham Thanh Tiep Tien Nguyen Jong-Hyuk Sung Simmyung Yook Jong Oh. Kim Chul Soon Yong Inho Choi Kyoung-Oh Doh Pil-Hoon Park Jun-Beom Park Yoojin Seo Bieong-Kil Kim Dong-Mok Lee Ik-Jae Moon Hyung-Sik Kim Jee-Heon Jeong |
| author_sort | Shobha Regmi |
| collection | DOAJ |
| description | Abstract 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. Conclusion 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. |
| first_indexed | 2024-12-23T05:17:35Z |
| format | Article |
| id | doaj.art-7f2d9c25befd4154adca588c99ed3e06 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-23T05:17:35Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-7f2d9c25befd4154adca588c99ed3e062022-12-21T17:58:46ZengBMCStem Cell Research & Therapy1757-65122019-10-0110111410.1186/s13287-019-1337-3Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicityShobha Regmi0Shiva Pathak1Tung Pham Thanh2Tiep Tien Nguyen3Jong-Hyuk Sung4Simmyung Yook5Jong Oh. Kim6Chul Soon Yong7Inho Choi8Kyoung-Oh Doh9Pil-Hoon Park10Jun-Beom Park11Yoojin Seo12Bieong-Kil Kim13Dong-Mok Lee14Ik-Jae Moon15Hyung-Sik Kim16Jee-Heon Jeong17College of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Yonsei UniversityCollege of Pharmacy, Keimyung UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Yeungnam UniversityDepartment of Medical Biotechnology, Yeungnam UniversityDepartment of Physiology, College of Medicine, Yeungnam UniversityCollege of Pharmacy, Yeungnam UniversityDepartment of Periodontics, College of Medicine, The Catholic University of KoreaDepartment of Life Science in Dentistry, School of Dentistry, Pusan National UniversityDepartment of Physiology, College of Medicine, Yeungnam UniversityBiomedical Manufacturing Technology Center, Korea Institute of Industrial TechnologyWELGENE Inc.Department of Life Science in Dentistry, School of Dentistry, Pusan National UniversityCollege of Pharmacy, Yeungnam UniversityAbstract 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. Conclusion 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.http://link.springer.com/article/10.1186/s13287-019-1337-3Mesenchymal stem cell2D-cultured cellsSpheroidsIntraportal deliveryFulminant hepatic failure |
| spellingShingle | Shobha Regmi Shiva Pathak Tung Pham Thanh Tiep Tien Nguyen Jong-Hyuk Sung Simmyung Yook Jong Oh. Kim Chul Soon Yong Inho Choi Kyoung-Oh Doh Pil-Hoon Park Jun-Beom Park Yoojin Seo Bieong-Kil Kim Dong-Mok Lee Ik-Jae Moon Hyung-Sik Kim Jee-Heon Jeong Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity Stem Cell Research & Therapy Mesenchymal stem cell 2D-cultured cells Spheroids Intraportal delivery Fulminant hepatic failure |
| title | Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity |
| title_full | Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity |
| title_fullStr | Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity |
| title_full_unstemmed | Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity |
| title_short | Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity |
| title_sort | intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against galn lps induced fulminant hepatic toxicity |
| topic | Mesenchymal stem cell 2D-cultured cells Spheroids Intraportal delivery Fulminant hepatic failure |
| url | http://link.springer.com/article/10.1186/s13287-019-1337-3 |
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