Healing cranial defects with AdRunx2-transduced marrow stromal cells.
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.
Program in Oral Health Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA.
Z
Z
Zhao
Z
Z
Wang
C
C
Ge
P
P
Krebsbach
R T
RT
Franceschi
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001861:Bone Regeneration / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D012886:Skull; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000637:transplantation; D014161:Transduction, Genetic; D014945:Wound Healing / Q000235:genetics
D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse