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Published as doi: 10.1096/fj.07-8275com.
 (The FASEB Journal. 2007;21:3917-3927.)
© 2007 FASEB
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Bone homing of mesenchymal stem cells by ectopic {alpha}4 integrin expression

Sanjay Kumar and Selvarangan Ponnazhagan1

Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA

1Correspondence: Department of Pathology, 701, 19th St. South, LHRB 513, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA. E-mail: pons{at}uab.edu

The pluripotent nature of mesenchymal stem cells (MSC) widens their potential for tissue regeneration and as vehicles for cell therapy in molecular medicine. Although the MSC are relatively easier to obtain and propagate in culture, a major impediment remains in their engraftment to target tissues on autologous transfer. We report here that transient, ectopic expression of {alpha}4 integrin (CD49d) on MSC greatly increases bone homing in an immunocompetent mouse model. Heterodimerization of the {alpha}4 integrin with endogenous β1 integrin (CD29) was confirmed to influence this targeting. In addition to retaining their stem cell property, the engrafted MSC were also found to form osteoblasts and osteocytes in the growth plate of recipient mouse limb bones (femur/tibia) in vivo. These findings provide evidence for a novel strategy to achieve bone homing of genetically engineered MSC, which may broadly benefit in targeted therapies for osteopenic bone defects and cancer bone metastasis.—Kumar, S., Ponnazhagan, S. Bone homing of mesenchymal stem cells by ectopic {alpha}4 integrin expression.


Key Words: tissue regeneration • cell therapy • bone targeting






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