A novel cell-free strategy for promoting mouse liver regeneration: utilization of a conditioned medium from adipose-derived stem cells
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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 × 106 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.
KeywordsAdipose-derived stem cells Mesenchymal stem cells Partial hepatectomy Secretome Liver regeneration
Adipose-derived stem cell
Mesenchymal stem cell
Polymerase chain reaction
Proliferating cell nuclear antigen
We thank Hurim Biocell Company for provision of human ASCs. We are also grateful to Hye Jin Jeong, Ok-Hee Kim, and Woo Joo Jung for technical assistance. We would like to thank Prof. Jong-Hoon Kim and his colleagues in Korea University for helpful discussions about these experiments. This work was supported by The Catholic University of Korea Daejeon St. Mary’s Hospital, with a Clinical Research Institute Grant (CMCDJ-A-2012).
Compliance with ethical requirements and Conflict of interest
All institutional and national guidelines for the care and use of laboratory animals were followed. Animal studies were carried out in compliance with the guidelines of the Institute for Laboratory Animal Research, Korea (IRB No: CMCDJ-AP-2013-006). Sang Kuon Lee, Sang Chul Lee, and Say-June Kim declare that they have no conflicts of interest or financial disclosure.
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