Gadherin-11 expression is upregulated in human adipose-derived stromal cells (hasc) over the course of osteogenio differentiation

摘要

Background Skeletal defects post significant challenges to surgeons in clinical settings with several diverse etiologies such as traumatic, congenital and malignant. Overall, the loss of bone, subsequent morbidity and clinical care that is delivered to address this problem pose a significant biomedical burden on the annual United States' healthcare economy that is estimated to exceed $7 billion. At the present time, clinicians employ a number of techniques to reconstruct and replace tissue where bone is missing. Autologous bone grafting is the gold standard to replace bone. In this approach, bone is harvested from one site in the body, such as split thickness calvarium, rib, fibula, and iliac crest, and used to bridge a bony gap elsewhere. While this uses a patient's own tissue, and avoids immunologic and infectious risks, this strategy may be associated with significant donor site morbidity including bleeding, infection, damage to surrounding tissues, wound healing problems, structural instability where bone was removed, and physical deformity or loss of cosmesis. Furthermore, limitations in quantity that may be harvested also exist. As an alternative to autologous bone, allogeneic and synthetic materials may also be used to reconstruct or replace skeletal tissue, but these therapies are also associated with factors that may limit or fetter their use, such as tendency to undergo resorption, nonintegration, expense, disease transmission, immunological issues including rejection, structural integrity, contouring abnormalities, hardware failure, and patient discomfort. As an alternative to tissue replacement, the current study suggests that it may be possible regenerate missing skeletal tissue. Human adipose-derived stromal cells (ASC) represent an autologous, abundant and accessible source of multipotent cells that may be used in cell-mediated tissue engineering applications for craniofacial bone. A number of studies in the animal model suggest that it is possible to regenerate bone with these multipotent precursors. It remains to be determined, however, whether their osteogenic capacity can be enhanced by means of gene therapy. One potential target may be Cadherin-11 (Cdh11), which is abundant in osteoblasts and mediates calcium-dependent cell-cell adhesion.5 This molecule has been shown to be a critical component of skeletal biology and bone homeostasis, and its upregulation in osteoblastic cell lines and stroma during differentiation, suggests a specific function in bone development and maintenance. Osteogenic differentiation of adipose-derived stromal cells is poorly understood, but the literature suggests many similarities to well-defined osteogenic models. As such, we were prompted to initiate investigations probing the role of Cdh 11 in accelerating or enhancing the osteogenic differentiation of hASC.