This grant was previously funded to explore the possibility of developing delivery vehicles to introduce bioactive factors into cartilage or bone repair sites. As part of that effort, we also previously proposed to develop the technology to deliver reparative cells to such cartilage or bone defects sites. With the departure of two primary investigators, Drs. Glenn Syftestad and Paul Lucas, to UC/Oavis, we have split this project into two separate, non- overlapping proposals to be reviewed separately. Drs. Syftestad and Lucas will continue with the bioactive factor delivery experiments and we will focus on the delivery of reparative cells. Because of this changing emphasis, Dr. Caplan has now assumed the role of Principal Investigator. We specifically propose to use our considerable experience with embryonic chick limb mesenchymal stem cells as a model for learning how to isolate, mitotically expand and characterize mesenchymal stem cells from bone marrow. Techniques will be specifically developed to isolate these marrow mesenchymal stem cells from adult donors using altered tissue culture substrates or monoclonal antibodies (McAbs) and to mitotically expand this cell-type 1n order to obtain enough cells to be used in massive repair circumstances. In this regard, we intend to test a cell delivery vehicle for bone repair designed to introduce marrow mesenchymal cells into a repair site for bone regeneration. The focus of this proposal is to learn about mesenchymal stem cells and how to manipulate them, develop markers for them (McAbs) and empirically learn how to reimplant these into a repair site for complete and appropriate regeneration of site-specific tissue. It is essential that the reparative cells be appropriately formatted to provide for optimal phenotypic differentiation and reparative integration of bone. In particular, the use of porous calcium phosphate ceramic filled with reparative cells has considerable potential use in cranial-facial reconstructions and in oral cavity prothesis anchorage. If successful, routine formulation of mesenchymal stem cells into reparative circumstances can be expected.
| Lazarus, H M; Haynesworth, S E; Gerson, S L et al. (1997) Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother 6:447-55 |
| Lazarus, H M; Haynesworth, S E; Gerson, S L et al. (1995) Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant 16:557-64 |
