Human adipose-derived mesenchymal stem cells promote recovery of injured HepG2 cell line and show sign of early hepatogenic differentiation
- 166 Downloads
Currently, orthotopic liver transplantation is the gold standard therapy for liver failure. However, it is limited by the insufficient organ donor and risk of immune rejection. Stem cell therapy is a promising alternative treatment for liver failure. One of the most ideal sources of stem cells for regenerative medicine is adipose-derived stem cells (ADSCs). In this study, primary ADSCs seeded on cell culture insert were indirectly co-cultured with injured HepG2 to elucidate the role of ADSCs in promoting the recovery of injured HepG2 in non-contact manner. HepG2 recovery was determined by the surface area covered by cells and growth factor concentration was measured to identify the factors involved in regeneration. Besides, HepG2 were collected for q-PCR analysis of injury, hepatocyte functional and regenerative markers expression. For the ADSCs, expression of hepatogenic differentiation genes was analyzed. Results showed that non-contact co-culture with ADSCs helped the recovery of injured HepG2. ELISA quantification revealed that ADSCs secreted higher amount of HGF and VEGF to help the recovery of injured HepG2. Furthermore, HepG2 co-cultured with ADSCs expressed significantly lower injury markers as well as significantly higher regenerative and functional markers compared to the control HepG2. ADSCs co-cultured with injured HepG2 expressed significantly higher hepatic related genes compared to the control ADSCs. In conclusion, ADSCs promote recovery of injured HepG2 via secretion of HGF and VEGF. In addition, co-cultured ADSCs showed early sign of hepatogenic differentiation in response to the factors released or secreted by the injured HepG2.
KeywordsNon-contact culture Adipose-derived stem cells Hepatocytes Hepatogenic differentiation Liver Regeneration
This work was supported by FRGS grant (Grant Number: UKM-FF-03-FRGS0165-2010) from Ministry of Higher Education (MOHE) of Malaysia.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Hayato K, Rie T, Takeshi K, Shumpei I, Tsuyoshi I et al (2015) Adipose tissue-derived mesenchymal stem cells in regenerative medicine treatment for liver cirrhosis—focused on efficacy and safety in preclinical and clinical studies. JSM Regen Med Bio Eng 3(1):1012Google Scholar
- Li GP, Wu LF, Pu ZJ (2008) Oxidative stress induces apoptosis in HepG2 cells. Chin J Pathophysiol 24:105–111. http://www.airitilibrary.com/Publication/alDetailedMesh?docid=10004718-200801-24-1-105-111-a Google Scholar
- Liau LL, Hui CK, Makpol S, Azurah AGN (2016) Hydrogen peroxide induces acute injury and up-regulates inflammatory gene expression in hepatocytes. Sains Malays 45:451–458Google Scholar
- Secunda R, Vennila R, Mohanashankar A, Rajasundari M, Jeswanth S, Surendran R (2015) Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: a comparative study. Cytotechnology 67:793–807CrossRefPubMedGoogle Scholar