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Modulation of BMP2-induced Calvarial Defect Healing Using Adipose, Bone Marrow, and Muscle-derived Stromal Cells
Shakir S, Wang D, Smith DM, Naran S, MacIsaac ZM, Losee JE, Cooper GM
University of Pittsburgh
2014-03-16
Presenter: Sameer Shakir
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting. This entire work represents the original work of Sameer Shakir and his co-authors.
Director Name: Joseph E. Losee
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: Craniomaxillofacial
PURPOSE: This study aims to determine the healing capacity of adipose (ADSC), bone marrow (BMDSC), and muscle-derived (MDSC) stromal cell populations in a calvarial defect model when this environment is optimized using bone morphogenetic protein 2 (BMP2). We hypothesize that BMP2 will augment stromal cell engraftment and differentiation within calvarial defects.
MATERIALS AND METHODS: Bone marrow, muscle, and adipose tissues were harvested from 10-week old wildtype mice (n=8). Cells were seeded overnight onto 5mm acellular dermal matrix (ADM) discs (1 x 105 cells/disc) and were osteoinduced with 150ng (30ng/mm2) BMP2. Unseeded ADM discs treated with either BMP2 or vehicle served as controls. Discs were subsequently placed into 5mm circular calvarial defects in 10-week old wildtype mice. Mice were euthanized 4 weeks postoperatively. Regenerate tissue was analyzed by 3D microCT and histology to assess percent healing and tissue morphology.
RESULTS: Percent healing was significantly decreased in BMP2 + stromal cell constructs and in vehicle control when compared to BMP2 therapy alone. BMP2 treated defects regenerated bone more morphologically more similar to native bone.
CONCLUSIONS: We observed significant modulation of BMP2-induced osteogenesis with the addition of stromal cells; unlike BMP2 therapy alone, osteoinduced stromal cell therapies do not improve defect healing beyond that of vehicle control in this model. These observations suggest that engrafted cells may be susceptible to environmental influences that determine their ability to contribute to cranial regeneration. We suggest that the inherently heterogeneous population of cells within the stroma of these tissues may restrict BMP2-induced calvarial defect healing.
