Sonic hedgehog gene-enhanced tissue engineering for bone regeneration

Abstract

Improved methods of bone regeneration are needed in the craniofacial rehabilitation of patients with significant bone deficits secondary to tumor resection, for congenital deformities, and prior to prosthetic dental reconstruction.

Deleterious Effects of Freezing on Osteogenic Differentiation of Human Adipose-Derived Stromal Cells In Vitro and In Vivo

“…The retinoid signaling pathway has likewise been thoroughly documented to enhance ASC osteogenesis [7,17,18]. Numerous studies have explored other signaling pathways in a candidate fashion to enhance ASC osteodifferentiation, including, but not limited to, connective tissue growth factor, insulin-like growth factor (IGF), and Hedgehog signaling [19][20][21]. The successful utilization of ASCs for skeletal tissue engineering hinges on a continued expansion of our understanding of those factors that both enhance and inhibit ASC osteogenic differentiation.…”

Tissue Engineering Craniofacial Defects With Adult Stem Cells? Are We Ready Yet?

“…However, the number of these studies does appear to be increasing as researchers turn to gene therapy approaches in the hopes of understanding and alleviating the disease state. For example, significant bone regeneration in a rabbit calvarial model has been measured upon implantation of MSCs transduced with Sonic Hedgehog (Shh)-a key protein involved in craniofacial morphogenesis (136). Although these results are promising, the stem cell population must be carefully considered as Shhexpressing ASCs were capable of regenerating bone within a calvarial defect but also appeared to induce the formation of large cyst-like structures.…”

The Pharmacology of Regenerative Medicine

“…Although these technologies lead to the production of therapeutic agents through more traditional pharmaceutical manufacturing methods (reactors, separation trains, and related quality control measures), the concept of using cells in situ to produce pharmaceutical agents is a more recent development. Examples of this approach range from the production of growth factors from cells within biomaterial scaffolds that take up viral or nonviral particles (Saul et al, 2007;De Laporte et al, 2010) to injecting cells with viral gene delivery particles in situ (Barton- Davis et al, 1998) to genetically engineering cells before implantation (Edwards et al, 2005). Each of these approaches ultimately leads to cell-based production of growth factors.…”