Approximately 500,000 bone-grafting procedures are performed each year in the United States (Boden 2002). Autologous iliac crest bone graft continues to be the gold standard because it provides the three essential elements for bone formation: osteoprogenitor cells, an osteoconductive matrix, and osteoinductive molecules. Iliac crest harvest is associated with a significant number of complications and often provides an inadequate volume of graft, however (Gupta 2001). To address these limitations, much work has been done to improve alternative grafts with better osteoconductive matrices and exogenous delivery of osteoinductive agents such as the bone morphogenetic proteins (BMPs) (Sykaras and Opperman 2003). In contrast, there are only a few basic point-of-care devices to isolate osteogenic progenitor cells, which are essential elements to foster bone healing. A device that could isolate stem cells from a bone marrow aspirate (BMA) at point of care would be of significant clinical benefit. In this phase II proposal, we will continue our development of a cell filtration device for the multipotent subpopulation of cells in human bone marrow known as mesenchymal stem cells (MSCs), which have been shown to promote healing of bone and soft tissue (Caplan and Bruder 2001). MSC-binding peptides have been isolated and used to capture MSCs from mixed cell populations. These MSC-binding peptides will be covalently attached to a solid support matrix and will form the functional core of the cell filtration device. MSCs isolated using our cell filtration device will be tested for improved bone healing. Elevated concentration of osteoprogenitor cells such as MSCs has been shown to improve bone healing in various animal models. Furthermore, an isolated pool of MSCs has the potential to serve key clinical functions in a range of indications including osteoarthritis, Chron's disease and soft tissue repair such as tendon, ligament or wounds. We feel this product will provide a point of care isolation system for the preparation of autologous cells, thereby eliminating the need for cultured or allogeneic stem cells. Our product will therefore provide a safer and more cost-effective source of stem cell therapy compared to currently available products containing MSCs.
Bone grafting is widely used in orthopedic surgery to treat fractures, large bone defects, and to achieve spinal fusions. Harvesting bone graft from patients is however associated with a significant number of complications and often provides an inadequate amount of tissue. Because of these limitations, much work has been done to improve alternative bone grafts using new bone scaffold materials and bone stimulating growth factors. These have shown promise, but there is still room for considerable improvement. There are only a few basic devices that isolate bone progenitor cells (MSCs), which are truly essential for bone healing. Therefore, a device, like the one proposed in this SBIR application, that could isolate MSCs efficiently and quickly in the operating room would be of significant clinical benefit in a number of clinical procedures.