Grants We Funded

Abstract
Limited availability and morbidity associated with suitable bone grafts has driven tissue engineering approaches to osseous repair. We plan to create a cellular based construct that will form structurally and functionally normal bone that is clinically applicable by studying the osteogenic potential of genetically manipulated human adipose derived stem cells (ASCs) within a 3-dimensional culture environment. Ideally, osteoprogenitor cells would be autologous, easily harvested, and would maintain strong osteogenic potential in patients of all ages. Although ASCs are abundant and easy to obtain/process, their potential for osteogenesis decreases with increasing donor age. It has been shown that ASCs can be reprogrammed by four virally transduced genes, Oct3/4, Sox2, Klf4, and c-Myc, to express embryonic stem cell (ESC) characteristics. By attaining an ESC-like state, induced ASCs (iASCs) may be able to not only increase bone formation but also maintain this response despite increasing donor age.
We plan to test our hypothesis by examining differences in proliferation and osteogenic potential between iASCs and control ASCs from the same donor. ASCs will be harvested from multiple donors allowing us to study the effect of increasing donor age. Lentiviral vectors containing the defined factors noted above and a lacZ marker will be used to transduce ASCs into iASCs which will be compared against appropriate controls. Population doubling time and DNA assays will be used to assess proliferative potential. Osteogenic differentiation will be determined by quantifying expression of osteogenic markers using RT-PCR, alkaline phosphatase assays, and Von Kossa mineralization. All experiments will be performed in both 2-D (PLGA film) and 3-D (PLGA Scaffold) cultures.
This work may provide further advance toward the creation of a clinically applicable bone graft substitute that can aid the plastic surgeon in the repair of bony defects.

Biography
Dr. Bradley is currently the Bernard Sarnat Professor of Plastic Surgery and Chief of Pediatric Plastic Surgery at the University of California, Los Angeles. He is also the Director of the Kawamoto Craniofacial Fellowship and Chief of Plastic Surgery at Olive View Medical Center. He is Board Certified by both the American Board of Plastic Surgery and the American Board of Surgery. Dr. Bradley received his Bachelor of Arts degree at the University of Notre Dame for Anthropology and Art. In Philadelphia, he matriculated at Thomas Jefferson Medical College where he received his Medical Degree. He then trained in General Surgery at Pennsylvania Hospital. In Manhattan, he completed his plastic surgery training at the Institute of Reconstructive Plastic Surgery, New York University. In Los Angeles, Dr. Bradley did additional training in Craniofacial Surgery at UCLA under Dr. Henry Kawamoto. In Pittsburgh, he directed the Craniofacial Surgery Program and was the Chief of Pediatric Plastic Surgery at the University for several years before returning to Los Angeles. Clinically, Dr. Bradley specializes in Craniofacial Surgery and volunteers internationally to help children with Craniofacial deformities. He is active in the bone tissue engineering laboratory at UCLA. He has published over 100 scientific papers, written over 20 chapters and edited 3 books. He also has a strong interest in not-for-profit foundation work aimed at children with facial deformities.