HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0513v1 25/3/798    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gottschling, S. Articles by Ho, A. D. Search for Related Content PubMed PubMed Citation Articles by Gottschling, S. Articles by Ho, A. D.

THE STEM CELL NICHE

Human Mesenchymal Stromal Cells Regulate Initial Self-Renewing Divisions of Hematopoietic Progenitor Cells by a β₁-Integrin-Dependent Mechanism

Department of Medicine V, Ruprecht-Karls University, Heidelberg, Germany

Key Words. Hematopoietic progenitor cells • Marrow stromal cells • Asymmetric cell division • Self-renewal • β₁-Integrins

Correspondence: Anthony D. Ho, M.D., Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Telephone: 49-6221-568001; Fax: 49-6221-5633639; e-mail: anthony_dick.ho{at}urz.uni-heidelberg.de

Received on August 16, 2006; accepted for publication on November 7, 2006.

First published online in STEM CELLS EXPRESS  November 16, 2006.


In previous reports, we have demonstrated that only direct cell-cell contact with stromal cells, such as the murine stromal cell line AFT024, was able to alter the cell division kinetics and self-renewing capacity of hematopoietic progenitor cells (HPC). Because β₁-integrins were shown to be crucial for the interaction of HPC with the bone marrow microenvironment, we have studied the role of β₁-integrins in the regulation of self-renewing cell divisions. For this purpose, we used primary human mesenchymal stromal (MS) cells as in vitro surrogate niche and monitored the division history and subsequent functional fate of individually plated CD34⁺133⁺ cells in the absence or presence of an anti-β₁-integrin blocking antibody by time-lapse microscopy and subsequent long-term culture-initiating cell (LTC-IC) assays. β₁-Integrin-mediated contact with MS cells significantly increased the proportion of asymmetrically dividing cells and led to a substantial increase of LTC-IC. Provided that β₁-integrin-mediated contact was available within the first 72 hours, human MS cells were able to recruit HPC into cell cycle and accelerate their division kinetics without loss of stem cell function. Activation of β₁-integrins by ligands alone (e.g., fibronectin and vascular cell adhesion molecule-1) was not sufficient to alter the cell division symmetry and promote self-renewal of HPC, thus indicating an indirect effect. These results have provided evidence that primary human MS cells are able to induce self-renewing divisions of HPC by a β₁-integrin-dependent mechanism.

This article has been cited by other articles:

				W. Wagner, C. Roderburg, F. Wein, A. Diehlmann, M. Frankhauser, R. Schubert, V. Eckstein, and A. D. Ho Molecular and Secretory Profiles of Human Mesenchymal Stromal Cells and Their Abilities to Maintain Primitive Hematopoietic Progenitors Stem Cells, October 1, 2007; 25(10): 2638 - 2647. [Abstract] [Full Text] [PDF]

				M. Yang, K. Li, P. C. Ng, C. K. Y. Chuen, T. K. Lau, Y. S. Cheng, Y. S. Liu, C. K. Li, P. Man Pan Yuen, A. Edward James, et al. Promoting Effects of Serotonin on Hematopoiesis: Ex Vivo Expansion of Cord Blood CD34+ Stem/Progenitor Cells, Proliferation of Bone Marrow Stromal Cells, and Antiapoptosis Stem Cells, July 1, 2007; 25(7): 1800 - 1806. [Abstract] [Full Text] [PDF]

				P. A. Schweizer, U. Krause, R. Becker, A. Seckinger, A. Bauer, C. Hardt, V. Eckstein, A. D. Ho, M. Koenen, H. A. Katus, et al. Atrial-Radiofrequency Catheter Ablation Mediated Targeting of Mesenchymal Stromal Cells Stem Cells, June 1, 2007; 25(6): 1546 - 1551. [Abstract] [Full Text] [PDF]