Bone homing of mesenchymal stem cells by ectopic alpha 4 integrin expression.
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 alpha4 integrin (CD49d) on MSC greatly increases bone homing in an immunocompetent mouse model. Heterodimerization of the alpha4 integrin with endogenous beta1 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
Sanjay
S
Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
Ponnazhagan
Selvarangan
S
D000818:Animals; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D039441:Integrin alpha4 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism
D019012:Integrin beta1; D039441:Integrin alpha4