PITA Fiscal Year 2010 Projects - Biomedical and Health Engineering

Stem Cell Delivery Using Platelet-Rich Plasma-Based Plastic Scaffolds

Principal Investigators: Phil Campbell, Lee Weiss

Effective delivery of stem cells into the body is one of the greatest challenges facing development of stem therapies for tissue repair and regeneration. Simple injection of cells into targeted tissue sites results in poor outcomes due to high cell mortality and surviving cells migrating away from the site of delivery. There is now compelling evidence that most stem cell therapies will require implantation of stem cells preseeded in 3D scaffolds as delivery and containment vehicles. We propose to use a porous scaffold biomaterial based on plasticized platelet-rich plasma for this application. These plasma-based plastics (PBPs) are comprised of naturally occurring constituents which the body is already designed to process, and thus this biomaterial is completely biocompatible for transplantation. Furthermore, these plastics not only have tailorable physical, mechanical and structural properties, but also provide a slowly-eluting cocktail of native hormones, growth factors, and nutrients which will nurture and cue the cells during cell attachment in vitro through to the initial stages of remodeling post implantation in vivo. Thus, PBPs will overcome many of the limitations of currently available scaffold biomaterial options. The aims of this research are to test and validate porous PBPs as a delivery scaffold for primary human bone marrow stem cells (BMSCs), which is a representative, clinically relevant adult stem cell population. First, we will assess stem cell seeding efficiencies, growth rates, maintenance of stemness, and differentiative potential in vitro for range of PBP material designs; cell activities within PBPs will be compared to traditional two-dimensional cell culture. Second, selected PBPs seeded with stem cells will then be implanted in a subcutaneous mouse model as a feasibility study to assess cell survival rates and retention within implanted constructs in vivo. Constructs with retained hormone and growth factor activities will be compared to constructs in which such activities have been destroyed.