Journal
FASEB JOURNAL
Volume 21, Issue 14, Pages 3917-3927Publisher
WILEY
DOI: 10.1096/fj.07-8275com
Keywords
tissue regeneration; cell therapy; bone targeting
Categories
Funding
- NCI NIH HHS [CA-98817] Funding Source: Medline
- NIAMS NIH HHS [AR-50251] Funding Source: Medline
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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 beta 1 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.
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