J Korean Soc Transplant.  2016 Mar;30(1):13-23. 10.4285/jkstn.2016.30.1.13.

Liver Regenerating Potential of the Secretome Obtained from Adipose-derived Stem Cells Cultured under the Hypoxic Environment

Affiliations
  • 1Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea. sayjunekim@gmail.com

Abstract

BACKGROUND
The stem cell-derived secretome has received considerable attention as an alternative to stem cells for therapeutic applications. However, establishing optimal culture conditions is key to obtaining appropriate secretome contents. Here, the optimal culturing environment for achieving a high-efficiency secretome was determined via hypoxic preconditioning of human adipose-derived stem cells (ASC).
METHODS
Normoxic conditioned media (NCM) and hypoxic conditioned media (HCM) were obtained after culturing human ASCs under normoxia (20% O2) or hypoxia (1% O2), respectively. Subsequently, both normal and thioacetamide-induced hepatotoxic hepatocytes were treated with NCM or HCM. In addition, partially hepatectomized mice were infused with control saline, NCM, and HCM. The effects on liver regeneration and serum transaminases levels were then compared.
RESULTS
Hypoxic preconditioning significantly increased mRNA expression of proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and growth factors (hepatocyte growth factor and vascular endothelial growth factor). In both normal and thioacetamide-induced hepatotoxic hepatocyte (alpha mouse liver 12 [AML12]) cell lines, HCM treatment resulted in the highest cell viability (122% and 95%, respectively), followed by NCM (111% and 78%, respectively). In addition, intravenous administration of HCM to partially hepatectomized mice resulted in substantially enhanced liver regeneration compared with the NCM group (P<0.05).
CONCLUSIONS
Taken together, the secretome obtained from ASC with hypoxic preconditioning showed potential to alleviate liver damage both in vitro and in vivo. Hypoxic culture of ASC is expected to play an important role in regenerative medicine by inducing secretome production that is beneficial for improving liver regeneration.

Keyword

Adipose-derived stem cell; Conditioned culture media; Hypoxic reconditioning; Liver regeneration; Paracrine effect; Secretome

MeSH Terms

Administration, Intravenous
Animals
Anoxia
Cell Line
Cell Survival
Culture Media, Conditioned
Cytokines
Hepatocytes
Humans
Intercellular Signaling Peptides and Proteins
Liver Regeneration
Liver*
Mice
Necrosis
Regenerative Medicine
RNA, Messenger
Stem Cells*
Transaminases
Culture Media, Conditioned
Cytokines
Intercellular Signaling Peptides and Proteins
RNA, Messenger
Transaminases
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