Tissue-Specific Stem Cells

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Multipotent Stromal Cells Are Activated to Reduce Apoptosis in Part by Upregulation and Secretion of Stanniocalcin-1†‡§

  1. Gregory J. Block1,
  2. Shinya Ohkouchi1,
  3. France Fung1,
  4. Joshua Frenkel1,
  5. Carl Gregory1,
  6. Radhika Pochampally1,
  7. Gabriel DiMattia2,
  8. Deborah E. Sullivan3,
  9. Darwin J. Prockop1,¶,*

Article first published online: 2 MAR 2009

DOI: 10.1634/stemcells.2008-0742

Issue

STEM CELLS

STEM CELLS

Volume 27, Issue 3, pages 670–681, March 2009

Additional Information

How to Cite

Block, G. J., Ohkouchi, S., Fung, F., Frenkel, J., Gregory, C., Pochampally, R., DiMattia, G., Sullivan, D. E. and Prockop, D. J. (2009), Multipotent Stromal Cells Are Activated to Reduce Apoptosis in Part by Upregulation and Secretion of Stanniocalcin-1. STEM CELLS, 27: 670–681. doi: 10.1634/stemcells.2008-0742

Author Information

  1. 1

    Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, Louisiana, USA

  2. 2

    London Regional Cancer Program and the Department of Oncology, Biochemistry, University of Western Ontario, London, Ontario, Canada

  3. 3

    Department of Microbiology and Immunology, Tulane University, New Orleans, Louisiana, USA

  1. Telephone: 504-988-7711 Fax: 504-988-7710

*Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, Louisiana, USA

  1. †

    Author contributions: G.J.B.: conception and design, collection and/or assembly of data, analysis and interpretation, manuscript writing and revisions; S.O.: conception and design, collection and/or assembly of data, analysis and interpretation, manuscript writing; F.F. and J.F.: collection of data; C.G. and R.P.: conception and design; G.D. and D.E.S.: conception and design, provision of study material or patients; D.J.P.: conception and design, analysis and interpretation, manuscript writing, final approval of manuscript. G.J.B. and S.O. contributed equally to this work.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSExpress December 18, 2008.

  4. Telephone: 504-988-7711 Fax: 504-988-7710

Publication History

  1. Issue published online: 2 MAR 2009
  2. Article first published online: 2 MAR 2009
  3. Manuscript Accepted: 3 DEC 2008
  4. Manuscript Received: 7 AUG 2008

Funded by

  • NIH. Grant Numbers: HL073755, HL073252, P01-HL075161
  • Louisiana Gene Therapy Research Consortium

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Keywords:

  • Multipotent stromal cells;
  • Stanniocalcin-1;
  • Apoptosis;
  • Ischemia;
  • UV irradiation;
  • Microarray

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. STEM CELLS2009;27:670–681

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