Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment: An experimental mouse model

Ok-Hee Kim; Ha-Eun Hong; Haeyeon Seo; Bong Jun Kwak; Ho Joong Choi; Kee-Hwan Kim; Joseph Ahn; Sang Chul Lee; Say-June Kim

doi:10.4252/wjsc.v12.i1.70

Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment: An experimental mouse model

World J Stem Cells. 2020 Jan 26;12(1):70-86. doi: 10.4252/wjsc.v12.i1.70.

Authors

Ok-Hee Kim¹, Ha-Eun Hong¹, Haeyeon Seo¹, Bong Jun Kwak², Ho Joong Choi², Kee-Hwan Kim¹, Joseph Ahn², Sang Chul Lee¹, Say-June Kim¹

Affiliations

¹ Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea.
² Department of Surgery, Division of Hepato-biliary Pancreatic Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea.

Abstract

Background: Recently, the exclusive use of mesenchymal stem cell (MSC)-secreted molecules, named as the secretome, have been evaluated for overcoming the limitations of cell-based therapy while maintaining its advantages.

Aim: To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.

Methods: We collected the secretory materials (named as inducers) released from AML12 hepatocytes that had been pretreated with thioacetamide (TAA) and generated the TAA-induced secretome (TAA-isecretome) after stimulating adipose-derived stem cells with the inducers. The TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial hepatectomy.

Results: TAA-isecretome infusion showed higher therapeutic potential in terms of (1) restoring disorganized hepatic tissue to normal tissue; (2) inhibiting proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α); and (3) reducing abnormally elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase) compared to the naïve secretome infusion in mice with TAA-induced hepatic failure. However, the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized mice. Proteomic analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the TAA-isecretome. In addition, peroxiredoxin-1, a potent antioxidant protein, was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic injury.

Conclusion: Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins, especially peroxiredoxin-1, with higher antioxidant activity. Our results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen. This approach is expected to open a new way of developing various specific therapeutics based on the high plasticity and responsiveness of MSCs.

Keywords: Adipose-derived stem cells; Disease-specificity; Mesenchymal stem cells; Peroxiredoxin-1; Secretome; Thioacetamide; Toxic hepatic failure.