Use of Adipose Derived Stem Cells to Treat Large Bone Defects. Addendum.

摘要

Trauma-induced injuries being sustained by our military men and women result in loss of multiple tissues, including associated vasculature and nerves. Current replacement technologies cannot address these kinds of injuries. Tissue engineering is still largely at the single cell stage and the tissues that are produced do not integrate well with surrounding tissues. Mesenchymal stem cells (MSCs) are an important tool but patients with large wounds may have reduced sources of stem cells and those stem cells that are present may be less robust as a consequence of trauma and medical treatment to suppress infection and inflammation. Our hypothesis is that effective repair of large defects requires the concerted processes of bone modeling and remodeling to create a functional marrow cavity, vascularization, and innervation and the best way to achieve this is by using autologous stem cells. Our objective is to develop technology to use adipose-derived MSCs to treat critical size segmental defects. Adipose-derived MSCs are attractive because of their relative abundance but there are still many issues that need to be resolved. We will: (1) develop methods for enriching the population of MSCs in adipose-derived cell preparations from rats; (2) determine if MSC-enriched adipose cells can be used to effectively treat large segmental defects using a rat segmental defect model developed in our group; and (3) optimize this technology for use in male and female animals. Adipose tissues from male and female normal Sprague Dawley rats and obese Zucker rats will be used as cell sources. MSCs will be enriched by selective removal of adipocytes and effectiveness will be determined using in vitro and in vivo assays. To test the ability of enriched MSCs to repair a critical size defect, cells will be loaded onto polymer composite scaffolds and implanted in a rat segmental defect (male in male; male in female; female in male; female in female) and healing assessed by various methods.