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Combinatorial Stem Cell Strategy for the Treatment of Liver Fibrosis

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Review of  “Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin-Expressing Adenovirus on Hepatic Fibrosis” from Stem Cells Translational Medicine by Stuart P. Atkinson

Progressive fibrosis, or scarring, of the liver can lead to cirrhosis, loss of liver function, and the onset of hepatocellular carcinoma and currently suffers from a lack of effective treatments. However, researchers from the laboratory of Soon Koo Baik (Yonsei University, Wonju, Republic of Korea) have sought to deal with this problem employing a novel type of combinatorial stem cell therapy.

This new strategy involved mesenchymal stem cells (MSCs), which the lab had previously found to improve hepatic fibrosis [1-3], expressing Decorin, a small leucine-rich proteoglycan which disrupts collagen fibril organization and prevents TGF-β1 binding to profibrotic receptors. In a new Stem Cells Translational Medicine study, the authors explore this combinatorial stem cell strategy for the improved treatment of liver fibrosis in a rat model [4].

The study first infected MSCs-derived from human bone marrow with a Decorin-expressing adenovirus or a control adenovirus before injection into fibrotic rat livers. While control (CA-) MSCs lowered the level of fibrosis, the Decorin-expressing (DCN-) MSCs reduced fibrosis to a lower level, as determined by various scoring systems (See figure, G2 = Untreated, G3 = CA-MSCs, G4 = DCN-MSCs). Overall, Decorin release from MSCs appeared to block TGF-β/Smad signaling in the liver to inhibit fibrotic responses, and, encouragingly, this also correlated to an increase in healthy liver function.

Great! This novel combinatorial stem cell strategy appears to have great promise in the treatment of liver fibrosis to inhibit the development of complications such as cirrhosis. However, as the authors note, the current adenoviral-mediated expression of Decorin may not be compatible with clinical translation to human patients, but they hope to employ further studies to determine viability.

References

  1. Jang YO, Kim MY, Cho MY, et al. Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model. BMC Gastroenterol 2014;14:198.
  2. Jang YO, Kim YJ, Baik SK, et al. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. Liver Int 2014;34:33-41.
  3. Jang YO, Jun BG, Baik SK, et al. Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis. Clin Mol Hepatol 2015;21:141-149.
  4. Jang YO, Cho MY, Yun CO, et al. Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin-Expressing Adenovirus on Hepatic Fibrosis. Stem Cells Transl Med 2016;5:1247-1256.