Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity

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

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Article number230
JournalStem Cell Research and Therapy
Issue number1
Publication statusPublished - 2019 Oct 16

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Korean Ministry of Science, ICT, and Future Planning (grant no. 2015R1A5A2009124 and 2018R1A5A2023879) and funded by the Ministry of Education (grant no. 2017R1D1A1B03027831); by the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI) and the Korean Ministry of Health and Welfare (grant no. HI18C0453); and by the Creative Economy Leading Technology Development Program through the Gyeongsangbuk-Do and Gyeongbuk Science and Technology Promotion Center of Korea (SF316001A).

Publisher Copyright:
© 2019 The Author(s).

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology


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