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Article first published online: 20 AUG 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 9, pages 1925–1937, September 2012
How to Cite
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. and Saito, I. (2012), Transplantation of side population cells restores the function of damaged exocrine glands through clusterin. STEM CELLS, 30: 1925–1937. doi: 10.1002/stem.1173
Author contributions: K.M. and I.S.: conception and design, Collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; H.I., T.N., Y.M., Y.A., F.I., M.M., H.Y., G.Y., J.T., R.Y., T.S., M.-C.-i.L., K.C., and H.S.: collection and assembly of data and final approval of manuscript; Y.K. and K.T.: data analysis and interpretation and final approval of manuscript; Y.M.: collection and assembly of data, data analysis and interpretation, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS July 10, 2012.
- Issue published online: 20 AUG 2012
- Article first published online: 20 AUG 2012
- Accepted manuscript online: 10 JUL 2012 04:16PM EST
- Manuscript Accepted: 14 JUN 2012
- Manuscript Received: 16 NOV 2011
- Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research
- Ministry of Health, Labor, and Welfare
- Side population cells;
- Cell transplantation;
- Cellular therapy;
- Endothelial cell
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. Stem Cells2012;30:1925–1937