Maxillofacial-derived stem cells regenerate critical mandibular bone defect.
Stem cell-based bone tissue regeneration in the maxillofacial complex is a clinical necessity. Genetic engineering of mesenchymal stem cells (MSCs) to follow specific differentiation pathways may enhance the ability of these cells to regenerate and increase their clinical relevance. MSCs isolated from maxillofacial bone marrow (BM) are good candidates for tissue regeneration at sites of damage to the maxillofacial complex. In this study, we hypothesized that MSCs isolated from the maxillofacial complex can be engineered to overexpress the bone morphogenetic protein-2 gene and induce bone tissue regeneration in vivo. To demonstrate that the cells isolated from the maxillofacial complex were indeed MSCs, we performed a flow cytometry analysis, which revealed a high expression of mesenchyme-related markers and an absence of non-mesenchyme-related markers. In vitro, the MSCs were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages. Gene delivery of the osteogenic gene BMP2 via an adenoviral vector revealed high expression levels of BMP2 protein that induced osteogenic differentiation of these cells in vitro and induced bone formation in an ectopic site in vivo. In addition, implantation of genetically engineered maxillofacial BM-derived MSCs into a mandibular defect led to regeneration of tissue at the site of the defect; this was confirmed by performing micro-computed tomography analysis. Histological analysis of the mandibles revealed osteogenic differentiation of implanted cells as well as bone tissue regeneration. We conclude that maxillofacial BM-derived MSCs can be genetically engineered to induce bone tissue regeneration in the maxillofacial complex and that this finding may be clinically relevant.
Steinhardt
Yair
Y
Skeletal Biotechnology Laboratory, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Aslan
Hadi
H
Regev
Eran
E
Zilberman
Yoram
Y
Kallai
Ilan
I
Gazit
Dan
D
Gazit
Zulma
Z
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001861:Bone Regeneration / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005147:Facial Bones / Q000166:cytology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008336:Mandibular Diseases / Q000503:physiopathology / Q000601:surgery*; D008437:Maxilla / Q000166:cytology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D055815:Young Adult