Published online Jan 26, 2020. doi: 10.4252/wjsc.v12.i1.70
Peer-review started: April 14, 2019
First decision: May 16, 2019
Revised: August 16, 2019
Accepted: September 26, 2019
Article in press: September 26, 2019
Published online: January 26, 2020
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.
To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.
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.
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.
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.
Core tip: Appropriate stimulation of adipose-derived stem cells with thioacetamide (TAA) led to the production of a secretome enriched with proteins, especially peroxiredoxin-1, with higher antioxidant activity. Free radicals are principal pathogenic agents in the pathogenesis of TAA-induced hepatic injury. The TAA-induced secretome was superior to the naïve secretome in restoring hepatic function while minimizing inflammatory processes in mice with TAA-induced hepatic failure. However, it was less effective in the mice with partial hepatectomy, suggestive of disease-specificity. Our results suggest that appropriate stimulation of adipose-derived stem cells with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen.