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TISSUE-SPECIFIC STEM CELLS |
Leopold Muller Arthritis Research Centre, School of Medicine, Keele University, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shrops, United Kingdom
Key Words. Mesenchymal stem cells • Homing • Adhesion molecules • Chemokine receptors • Differentiation • Immunobiology
Correspondence: Jim Middleton, Ph.D., Leopold Muller Arthritis Research Centre, School of Medicine, Keele University, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shrops SY10 7AG, U.K. Telephone: 01691 404149; Fax: 01691 404170; e-mail: jim.middleton{at}rjah.nhs.uk
Received March 21, 2007;
accepted for publication July 17, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS July 26, 2007.
MSCs are nonhematopoietic stromal cells that are capable of differentiating into, and contribute to the regeneration of, mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and adipose. MSCs are rare in bone marrow, representing
1 in 10,000 nucleated cells. Although not immortal, they have the ability to expand manyfold in culture while retaining their growth and multilineage potential. MSCs are identified by the expression of many molecules including CD105 (SH2) and CD73 (SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. The properties of MSCs make these cells potentially ideal candidates for tissue engineering. It has been shown that MSCs, when transplanted systemically, are able to migrate to sites of injury in animals, suggesting that MSCs possess migratory capacity. However, the mechanisms underlying the migration of these cells remain unclear. Chemokine receptors and their ligands and adhesion molecules play an important role in tissue-specific homing of leukocytes and have also been implicated in trafficking of hematopoietic precursors into and through tissue. Several studies have reported the functional expression of various chemokine receptors and adhesion molecules on human MSCs. Harnessing the migratory potential of MSCs by modulating their chemokine-chemokine receptor interactions may be a powerful way to increase their ability to correct inherited disorders of mesenchymal tissues or facilitate tissue repair in vivo. The current review describes what is known about MSCs and their capacity to home to tissues together with the associated molecular mechanisms involving chemokine receptors and adhesion molecules.
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