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: 2005-0319v1 24/4/1030    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 Google Scholar Google Scholar Articles by Honczarenko, M. Articles by Silberstein, L. E. Search for Related Content PubMed PubMed Citation Articles by Honczarenko, M. Articles by Silberstein, L. E.

TISSUE-SPECIFIC STEM CELLS

Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

^a Joint Program in Transfusion Medicine, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA;
^b Divisions of Allergy-Inflammation and Infectious Diseases at the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Key Words. Stromal cells • Chemokines • Transplantation • Migration • Bone marrow microenvironment

Correspondence: Leslie E. Silberstein, M.D., Joint Program in Transfusion Medicine, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Bldg, RB10217, 1 Blackfan Circle, Boston, Massachusetts 02115, USA. Telephone: 617-919-2588; Fax: 617-730-0615; e-mail: leslie.silberstein{at}childrens.harvard.edu

Received July 14, 2005; accepted for publication October 20, 2005.
Stromal cells isolated from bone marrow (BMSCs), often referred to as mesenchymal stem cells, are currently under investigation for a variety of therapeutic applications. However, limited data are available regarding receptors that can influence their homing to and positioning within the bone marrow. In the present study, we found that second passage BMSCs express a unique set of chemokine receptors: three CC chemokine receptors (CCR1, CCR7, and CCR9) and three CXC chemokine receptors (CXCR4, CXCR5, and CXCR6). BMSCs cultured in serum-free medium secrete several chemokine ligands (CCL2, CCL4, CCL5, CCL20, CXCL12, CXCL8, and CX₃CL1). The surface-expressed chemokine receptors were functional by several criteria. Stimulation of BMSCs with chemokine ligands triggers phosphorylation of the mitogen-activated protein kinase (e.g., extracellular signal–related kinase [ERK]-1 and ERK-2) and focal adhesion kinase signaling pathways. In addition, CXCL12 selectively activates signal transducer and activator of transcription (STAT)-5 whereas CCL5 activates STAT-1. In cell biologic assays, all of the chemokines tested stimulate chemotaxis of BMSCs, and CXCL12 induces cytoskeleton F-actin polymerization. Studies of culture-expanded BMSCs, for example, 12–16 passages, indicate loss of surface expression of all chemokine receptors and lack of chemotactic response to chemokines. The loss in chemokine receptor expression is accompanied by a decrease in expression of adhesion molecules (ICAM-1, ICAM-2, and vascular cell adhesion molecule 1) and CD157, while expression of CD90 and CD105 is maintained. The change in BMSC phenotype is associated with slowing of cell growth and increased spontaneous apoptosis. These findings suggest that several chemokine axes may operate in BMSC biology and may be important parameters in the validation of cultured BMSCs intended for cell therapy.