Gary Balian, Ph.D.

Mary Muilenburg Stamp Professor of Orthopaedic Research and Professor of Biochemistry and Molecular Genetics

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 which 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 which are needed for skeletal growth, thereby leading to recovery from bone loss and improved bone growth and repair. Attempts are underway to deliver growth actor genes such as insulin growth factor-1 (IFG-1) and vascular endothelial growth factor (VEGF) by transfecting pluripotential marrow cells with IFG-1 or VEGF cDNA. Appropriately selected promoters coupled with the homing properties of the marrow cells to bone and to sites of bone repair and tissue regeneration are being used as a basis for the experiments. These are designed to increase vascularization at sites of injury, such as fractures, in order to enhance the process of endochondral ossification. The objectives are to develop techniques which incorporate cellular therapy and gene deliver as possible treatments for non-unions, fixation of prostheses, the management of osteoporosis, and for metastatic cancer therapy.

Currently, 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 transplanted marrow cells to bone ingrowth and adhesion to metal implants.
  3. Marrow cell involvement in fracture repair and bone regeneration.
  4. Deliver of growth factor genes using transfected pluripotent cells to induce articular cartilage regeneration and bone repair.
  5. Combined cell and gene therapy of metastatic cancer.

Selected Publications:

Topping, R.E., Bolander, M.E. and Balian, G.: Type X collagen in fracture callus is decreased in experimental diabetes. Clin Orthop. Rel. Res., 308:220-228, 1994.

Schwartz, Z., Hancock, R.H., Dean, D.D., Brooks, B.P., Gomez, r., Boskey, A.L., Balian, G. and Boyan, B.D.: Dexamethasone promotes von Kossa-positive nodule formation and increased alkaline phosphatase activity in costochondral chondrocyte cultures. Endocrine 3:351-360, 1995.

Cui, Q., Wang, G-J., Balian, G.: Steroid-induced adipogenesis in a pluripotential cell line from bone marrow. J Bone & Joint Surg 79-A:1054-1063, 1997.

Cui, Q., Wang, G-J., Su, C.C., Balian, G.: Lovastatin prevents steroid-induced adipogenesis and osteonecrosis. The Otto E. Aufranc Award. Clin Orthop Rel Res 344:8-19, 1997.

Fujioka, H., Wang, G-J., Mizuno, K., Balian, G., Hurwitz, S.R.: Changes in the expression of type-X collagen in the fibrocartilage of rat achilles tendon attachment during development. J Ortho Res. 15(5):675-681, 1997.

Fujioka, H., Thakur, R., Wang, G-J., Mizuno, K., Balian, G., Hurwitz, S.R.: Comparison of surgically attached and non-attached repair of the rat achilles tendon-bone interface. Cellular organization and type X collagen expression. Conn Tiss Res 37(3-4):205-218, 1998.

Wu, T.T., Sikes, R.A., Cui, Q., Thalmann, G.N., Kao, C., Murphy, C.F., Yang, H., Zhau, H.E., Balian, G., Chung, L.W.K.: Establishing human prostate cancer cell xenografts in bone: Induction of osteoblastic reaction by PSA-producing tumors in athymic and SCID/bg mice using LNcaP and lineage-derived metastatic sublines. Intl J Cancer, 77:887-894, 1998.

Lim, A., Doyle, S.A., Balian, G., Smith, B.D.: The role of the Pro-a2(l) COOH-terminal region in assembly of type I collagen: Truncation of the last ten amino acid residues of Pro-a2(l) chain prevents the assembly of type I collagen heterotrimer. J. Cellular Physiology. 71:216-232, 1998.