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Paracrine Interaction between Adipose-Derived Stromal Cells and Cranial Suture–Derived Mesenchymal Cells

James, Aaron W. M.D.; Levi, Benjamin M.D.; Commons, George W. M.D.; Glotzbach, Jason M.D.; Longaker, Michael T. M.D., M.B.A.

Plastic and Reconstructive Surgery: September 2010 - Volume 126 - Issue 3 - p 806-821
doi: 10.1097/PRS.0b013e3181e5f81a
Experimental: Original Articles

Background: Adipose-derived stromal cells are a potential cell source for the successful healing of skeletal defects. In this study, the authors sought to investigate the potential for cranial suture-derived mesenchymal cells to promote the osteogenic differentiation of adipose-derived stromal cells. Various reports have previously examined the unique in vitro attributes of suture-derived mesenchymal cells; this study sought to extend those findings.

Methods: Suture-derived mesenchymal cells were isolated from wild-type mice (n = 30) from both fusing posterofrontal and patent sagittal sutures. Cells were placed in Transwell inserts with human adipose-derived stromal cells (n = 5 patients) with osteogenic differentiation medium with or without recombinant Noggin (10 to 400 ng/ml). Specific gene expression of osteogenic markers and Hedgehog pathway were assayed; standard osteogenic assays (alkaline phosphatase and alizarin red staining) were performed. All assays were performed in triplicate.

Results: Both posterofrontal and sagittal suture-derived mesenchymal cells induced osteogenic differentiation of adipose-derived stromal cells (p < 0.05). Posterofrontal suture-derived mesenchymal cells induced adipose-derived stromal cell osteogenesis to a greater degree than sagittal suture-derived mesenchymal cells (p < 0.05). This was accompanied by an increase in bone morphogenetic protein expression (p < 0.05). Finally, recombinant Noggin mitigated the pro-osteogenic effects of co-culture accompanied by a reduction in Hedgehog signaling (p < 0.05).

Conclusions: Suture-derived mesenchymal cells secrete paracrine factors that induce osteogenic differentiation of multipotent stromal cells (human adipose-derived stromal cells). Cells derived from the fusing posterofrontal suture do this to a significantly greater degree than cells from the patent sagittal suture. Enhanced bone morphogenetic protein and Hedgehog signaling may underlie this paracrine effect.

Stanford, Calif.

From the Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine.

Received for publication December 21, 2009; accepted March 10, 2010.

The first two authors share first authorship for the work presented in this article.

Disclosure: The authors have no commercial associations or financial disclosures that might pose or create a conflict of interest with information presented in this article.

Michael T. Longaker, M.D., M.B.A., Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, Calif. 94305-5148,

©2010American Society of Plastic Surgeons