IFATS collection: In vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury

Agnieszka Banas, Takumi Teratani, Yusuke Yamamoto, Makoto Tokuhara, Fumitaka Takeshita, Mitsuhiko Osaki, Masaki Kawamata, Takashi Kato, Hitoshi Okochi, Takahiro Ochiya

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs), largely present in the adult human body, represent an attractive tool for the establishment of a stem cell-based therapy for liver diseases. Recently, the therapeutic potential and immunomodulatory activity of MSCs have been revealed. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), so-called adipose-derived stem cells or adipose stromal cells, because of their high accessibility with minimal invasiveness, are especially attractive in the context of future clinical applications. The goal of the present study was to evaluate the therapeutic potential of AT-MSCs by their transplantation into nude mice with CCl4-caused liver injury. We observed that after transplantation, AT-MSCs can improve liver functions, which we verified by changes in the levels of biochemical parameters. Ammonia, uric acid, glutamic-pyruvic transaminase, and glutamic-oxaloacetic transaminase concentrations returned to a nearly normal level after AT-MSC transplantation. These results raised the question of how AT-MSCs can achieve this. To discover the possible mechanisms involved in this therapeutic ability of AT-MSCs, in vitro production of cytokines and growth factors was analyzed and compared with MSCs from bone marrow (BM-MSCs) and normal human dermal fibroblasts (NHDFs). As a result we observed that AT-MSCs secrete interleukin 1 receptor α (IL-1Rα), IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 1, nerve growth factor, and hepatocyte growth factor in a volume higher than both BMMSCs and NHDFs. Thus, our findings suggest that ATMSCs may account for their broad therapeutic efficacy in animal models of liver diseases and in the clinical settings for liver disease treatment.

Original languageEnglish
Pages (from-to)2705-2712
Number of pages8
JournalSTEM CELLS
Volume26
Issue number10
DOIs
Publication statusPublished - 2008 Oct 1

Keywords

  • Adipose
  • Liver function
  • Liver regeneration
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Banas, A., Teratani, T., Yamamoto, Y., Tokuhara, M., Takeshita, F., Osaki, M., Kawamata, M., Kato, T., Okochi, H., & Ochiya, T. (2008). IFATS collection: In vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. STEM CELLS, 26(10), 2705-2712. https://doi.org/10.1634/stemcells.2008-0034