FTY720 Promotes Local Microvascular Network Formation and Regeneration of Cranial Bone Defects
Year: 2009
Type: article
Abstract: The calvarial bone microenvironment contains a unique progenitor niche that should be considered for therapeutic manipulation when designing regeneration strategies. Recently, our group demonstrated that cells isolated from the dura are multipotent and exhibit expansion potential and robust mineralization on biodegradable constructs in vitro. In this study, we evaluate the effectiveness of healing critical-sized cranial bone defects by enhancing microvascular network growth and host dura progenitor trafficking to the defect space pharmacologically by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P(1) and S1P(3) significantly increase bone ingrowth, total microvessel density, and smooth muscle cell investment on nascent microvessels within the defect space. Further, in vitro proliferation and migration studies suggest that selective activation of S1P(3) promotes recruitment and growth of osteoblastic progenitors from the meningeal dura mater.
Source: Tissue Engineering Part A
Institution: University of Virginia
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, American Heart Association, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research
Awards: G2758903446, Phospholipid Growth Factors for Therapeutic Arteriogenesis and Tissue Engineering, Therapeutic S1P Drug Targets for Cranial Bone Repair, G3811511043, G5786033734, Vascularized Bone Grafts for Tissue Engineering, REGULATION OF CRANIALSUTURE MORPHOGENESIS, Biotechnology Training Grant, Arteriole/Venule Polarity in Adult Microvasculature
OpenAlex ID: W2093512399
