A novel cell-free strategy for promoting mouse liver regeneration: utilization of a conditioned medium from adipose-derived stem cells.

Abstract

Although stem cells have beneficial effects, their clinical application faces many issues, including high cost and safety. Because stem cell plasty is largely based on their paracrine activity, this study aimed to test the hypothesis that utilization of the stem-cell secretome instead of actual cells would not only overcome these limitations, but also have similar effects as stem cell-based therapy. Partial hepatectomized mice were divided into four groups according to the material administered via the tail vein: normal saline (saline group); 1.0 × 10(6) human adipose tissue-derived stem cells (ASCs) in 0.1 mL saline (ASC group); 25-fold concentrated conditioned medium from ASCs (ASC-secretome group); and concentrated medium (media group). Specimens were obtained postoperatively. Liver regeneration was estimated by bromodeoxyuridine incorporation, Lgr5 RT-PCR, proliferating cell nuclear antigen western blot, and liver weights, and liver function was estimated by albumin immunohistochemistry and liver function tests. The liver regenerative capacities of the ASC and ASC-secretome groups were not statistically different from each other, but were higher than their respective control groups. Moreover, the ASC and ASC-secretome groups promoted the phosphorylation of Akt, STAT3, and Erk1/2, and expressed higher levels of mouse albumin in immunohistochemistry. ASCs and ASC-secretome infusions to the partially hepatectomized mice produced similar outcomes in terms of liver regeneration and mouse albumin expression. Therefore, cell-free therapy, which is based on the paracrine properties of stem cells, is expected to overcome the limitations of cell-based methods and to provide a novel treatment for liver diseases.