Transplantation of side population cells restores the function of damaged exocrine glands through clusterin

Kenji Mishima, Hiroko Inoue, Tatsuaki Nishiyama, Yo Mabuchi, Yusuke Amano, Fumio Ide, Makoto Matsui, Hiroyuki Yamada, Gou Yamamoto, Junichi Tanaka, Rika Yasuhara, Takashi Sakurai, Masaichi Chang Il Lee, Kan Chiba, Hidetoshi Sumimoto, Yutaka Kawakami, Yumi Matsuzaki, Kazuo Tsubota, Ichiro Saito

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24 Citations (Scopus)

Abstract

Stem cell-based therapy has been proposed as a promising strategy for regenerating tissues lost through incurable diseases. Side population (SP) cells have been identified as putative stem cells in various organs. To examine therapeutic potential of SP cells in hypofunction of exocrine glands, SP cells isolated from mouse exocrine glands, namely, lacrimal and salivary glands, were transplanted into mice with irradiation-induced hypofunction of the respective glands. The secretions from both glands in the recipient mice were restored within 2 months of transplantation, although the transplanted cells were only sparsely distributed and produced no outgrowths. Consistent with this, most SP cells were shown to be CD31-positive endothelial-like cells. In addition, we clarified that endothelial cell-derived clusterin, a secretory protein, was an essential factor for SP cell-mediated recovery of the hypofunctioning glands because SP cells isolated from salivary glands of clusterin-deficient mice had no therapeutic potential, whereas lentiviral transduction of clusterin restored the hypofunction. In vitro and in vivo studies showed that clusterin had an ability to directly inhibit oxidative stress and oxidative stress-induced cell damage. Thus, endothelial cell-derived clusterin possibly inhibit oxidative stress-induced hypofunction of these glands.

Original languageEnglish
Pages (from-to)1925-1937
Number of pages13
JournalStem Cells
Volume30
Issue number9
DOIs
Publication statusPublished - 2012 Sep

Keywords

  • Cell transplantation
  • Cellular therapy
  • Endothelial cell
  • Side population cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Mishima, K., Inoue, H., Nishiyama, T., Mabuchi, Y., Amano, Y., Ide, F., Matsui, M., Yamada, H., Yamamoto, G., Tanaka, J., Yasuhara, R., Sakurai, T., Lee, M. C. I., Chiba, K., Sumimoto, H., Kawakami, Y., Matsuzaki, Y., Tsubota, K., & Saito, I. (2012). Transplantation of side population cells restores the function of damaged exocrine glands through clusterin. Stem Cells, 30(9), 1925-1937. https://doi.org/10.1002/stem.1173