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Biological

Healing Cranial Defects with AdRunx2-transduced Marrow Stromal Cells

Z. Zhao1,2, Z. Wang3, C. Ge2, P. Krebsbach3 and R.T. Franceschi2,4,*

1 Program in Oral Health Sciences,
2 Department of Periodontics and Oral Medicine, and
3 Department of Biological and Material Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; and
4 Department of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USA

Correspondence: * corresponding author, rennyf{at}umich.edu

Marrow stromal cells (MSCs) include stem cells capable of forming all mesenchymal tissues, including bone. However, before MSCs can be successfully used in regeneration procedures, methods must be developed to stimulate their differentiation selectively to osteoblasts. Runx2, a bone-specific transcription factor, is known to stimulate osteoblast differentiation. In the present study, we tested the hypothesis that Runx2 gene therapy can be used to heal a critical-sized defect in mouse calvaria. Runx2-engineered MSCs displayed enhanced osteogenic potential and osteoblast-specific gene expression in vitro and in vivo. Runx2-expressing cells also dramatically enhanced the healing of critical-sized calvarial defects and increased both bone volume fraction and bone mineral density. These studies provide a novel route for enhancing osteogenesis that may have future therapeutic applications for craniofacial bone regeneration.

Key Words: adenovirus • bone • regeneration • gene therapy • Runx2 • stem cells

Journal of Dental Research, Vol. 86, No. 12, 1207-1211 (2007)
DOI: 10.1177/154405910708601213
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