Original Article

Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn's disease†

  1. Wojciech Marlicz MD, PhD1,
  2. Ewa Zuba-Surma PhD2,
  3. Magda Kucia PhD3,
  4. Wojciech Blogowski MD4,
  5. Teresa Starzynska MD, PhD1,
  6. Mariusz Z. Ratajczak MD, PhD3,5,*

Article first published online: 11 JAN 2012

DOI: 10.1002/ibd.22875

Issue

Inflammatory Bowel Diseases

Inflammatory Bowel Diseases

Volume 18, Issue 9, pages 1711–1722, September 2012

Additional Information

How to Cite

Marlicz, W., Zuba-Surma, E., Kucia, M., Blogowski, W., Starzynska, T. and Ratajczak, M. Z. (2012), Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn's disease. Inflamm Bowel Dis, 18: 1711–1722. doi: 10.1002/ibd.22875

Author Information

  1. 1

    Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland

  2. 2

    Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland

  3. 3

    Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Kentucky

  4. 4

    Department of Laboratory and Molecular Medicine, Pomeranian Medical University, Szczecin, Poland

  5. 5

    Department of Physiology, Pomeranian Medical University, Szczecin, Poland

*Hoenig Endowed Chair, Professor and Director Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd St., Rm. 107, Louisville, KY 40202

  1. †

    Supported by a grant from EU structural funds, Innovative Economy Operational Program POIG.01.01.02-00-109/09.

Publication History

  1. Issue published online: 9 AUG 2012
  2. Article first published online: 11 JAN 2012
  3. Manuscript Accepted: 12 DEC 2011
  4. Manuscript Received: 29 NOV 2011

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Keywords:

  • stem cells;
  • IBD;
  • mobilization;
  • VSELs

Abstract

Background:

Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue/organ injury. We sought to determine whether these cells are mobilized into PB in patients with Crohn's disease (CD).

Methods:

Twenty-five patients with active CD, 20 patients in clinical remission, and 25 age-matched controls were recruited and PB samples harvested. The circulating CD133+/Lin−/CD45+ and CD34+/Lin−/CD45+ cells enriched for HSPCs, CD105+/STRO-1+/CD45− cells enriched for MSCs, CD34+/KDR+/CD31+/CD45−cells enriched for EPCs, and small CXCR4+CD34+CD133+ subsets of Lin−CD45− cells that correspond to the population of VSELs were counted by fluorescence-activated cell sorting (FACS) and evaluated by direct immunofluorescence staining for pluripotency embryonic markers and by reverse-transcription polymerase chain reaction (RT-PCR) for expression of messenger (m)RNAs for a panel of genes expressed in intestine epithelial stem cells. The serum concentration of factors involved in stem cell trafficking, such as stromal derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were measured by enzyme-linked immunosorbent assay (ELISA).

Results:

Our data indicate that cells expressing markers for MSCs, EPCs, and small Oct-4+Nanog+SSEA-4+CXCR4+lin−CD45− VSELs are mobilized into PB in CD. The mobilized cells also expressed at the mRNA level genes playing a role in development and regeneration of gastrointestinal epithelium. All these changes were accompanied by increased serum concentrations of VEGF and HGF.

Conclusions:

CD triggers the mobilization of MSCs, EPCs, and VSELs, while the significance and precise role of these mobilized cells in repair of damaged intestine requires further study. (Inflamm Bowel Dis 2012;)

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