Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1

Gregory J. Block, Shinya Ohkouchi, France Fung, Joshua Frenkel, Carl Gregory, Radhika Pochampally, Gabriel Dimattia, Deborah E. Sullivan, Darwin J. Prockop

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166 Citations (Scopus)

Abstract

Multipotent stromal cells (MSCs) have been shown to reduce apoptosis in injured cells by secretion of paracrine factors, but these factors were not fully defined. We observed that coculture of MSCs with previously UV-irradiated fibroblasts reduced apoptosis of the irradiated cells, but fresh MSC conditioned medium was unable reproduce the effect. Comparative microarray analysis of MSCs grown in the presence or absence of UV-irradiated fibroblasts demonstrated that the MSCs were activated by the apoptotic cells to increase synthesis and secretion of stanniocalcin-1 (STC-1), a peptide hormone that modulates mineral metabolism and has pleiotrophic effects that have not been fully characterized. We showed that STC-1 was required but not sufficient for reduction of apoptosis of UV-irradiated fibroblasts. In contrast, we demonstrated that MSC- derived STC-1 was both required and sufficient for reduction of apoptosis of lung cancer epithelial cells made apoptotic by incubation at low pH in hypoxia. our data demonstrate that STC-1 mediates the antiapoptotic effects of MSCs in two distinct models of apoptosis in vitro.

Original languageEnglish
Pages (from-to)670-681
Number of pages12
JournalStem Cells
Volume27
Issue number3
DOIs
Publication statusPublished - 2009 Mar 1
Externally publishedYes

Keywords

  • Apoptosis, ischemia
  • Microarray
  • Multipotent stromal cells
  • Stanniocalcin-1
  • UV irradiation

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Block, G. J., Ohkouchi, S., Fung, F., Frenkel, J., Gregory, C., Pochampally, R., Dimattia, G., Sullivan, D. E., & Prockop, D. J. (2009). Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1. Stem Cells, 27(3), 670-681. https://doi.org/10.1634/stemcells.2008-0742