A number of macromolecules are synthesized by cells and secreted into the extracellular environment where they are involved in the organization of the matrix around the cells. The molecules vary according to the type of cells that are under investigation. Their properties are essential and sometimes specific to the tissues from which the cells are derived. Thus, the interactions of extracellular macromolecules with each other and with the cell surface can influence the behavior of cells during development.

The expression of genes that code for specific molecules is also developmentally regulated. The synthesis of extracellular macromolecules and their assembly outside cells determine to a large extent their role in normal morphogenesis and in tissue repair.

Precursor cells isolated from bone marrow develop into a variety of cell types which contribute to skeletal growth and repair. The osteogenic phenotype of these precursor cells is relevant to the process of fracture healing and bone growth into prosthetic implants. Cells that are cloned from marrow stroma repopulate the marrow of host mice, persist for several weeks and retain their osteogenic potential. Such cells may be used to replenish the number of osteoprogenitors in marrow, which diminish with age, and to deliver factors that are needed for skeletal growth, thereby leading to recovery from bone loss and improved bone growth and repair. The objectives are to develop cellular therapy and gene delivery as possible treatments for non-unions, fixation of prostheses and the management of osteoporosis.

Based on the homing mechanism of the marrow cells, collaboration has been established to develop the pluripotential cells as a vehicle to deliver therapeutic genes to cancer metastases in bone.

In addition, several research projects are being pursued in this program. 1. The role of pluripotent mesenchymal cells in marrow during steroid-induced adipogenesis and the ensuing osteonecrosis and osteoporosis. 2. The contribution of marrow cells to bone ingrowth and adhesion to titanium implants after intravenous and intramedullary transplantation. 3. Marrow cell involvement in fracture repair and bone regeneration in cortical defects. 4. Delivery of growth factor genes using transfected pluripotent cells to induce articular cartilage regeneration and bone repair.

Selected References

Cui Q, Wang GJ, Balian G. (1997) "Steroid-induced adipogenesis in a pluripotential cell line from bone marrow." J Bone Joint Surg Am. 79:1054-63. [PubMed]

Fujioka H, Wang GJ, Mizuno K, Balian G, Hurwitz SR. (1997) "Changes in the expression of type-X collagen in the fibrocartilage of rat Achilles tendon attachment during development." J Orthop Res. 15:675-81. [PubMed]

Fujioka H, Thakur R, Wang GJ, Mizuno K, Balian G, Hurwitz SR. (1998) "Comparison of surgically attached and non-attached repair of the rat Achilles tendon-bone interface. Cellular organization and type X collagen expression." Connect Tissue Res. 37(3-4):205-18. [PubMed]

Dahir GA, Cui Q, Anderson P, Simon C, Joyner C, Triffitt JT, Balian G. (2000) "Pluripotential mesenchymal cells repopulate bone marrow and retain osteogenic properties." Clin Orthop Relat Res. (379 Suppl):S134-45. [PubMed]

Cui Q, Wang GJ, Balian G. (2000) "Pluripotential marrow cells produce adipocytes when transplanted into steroid-treated mice." Connect Tissue Res. 41:45-56. [PubMed]

Gooch HL, Hale JE, Fujioka H, Balian G, Hurwitz SR. (2000) "Alterations of cartilage and collagen expression during fracture healing in experimental diabetes." Connect Tissue Res. 41:81-91. [PubMed]

Wang GJ, Cui Q, Balian G. (2000) "The Nicolas Andry award. The pathogenesis and prevention of steroid-induced osteonecrosis." Clin Orthop Relat Res. (370):295-310. [PubMed]