Brian Johnstone, Ph.D.
Adjunct Professor, Department of Orthopaedics and Rehabilitation
Biography
Dr. Johnstone received his B.Sc. degree in Applied Biochemistry from Brunel University, Middlesex, England in 1983. He conducted his predoctoral research at the Kennedy Institute of Rheumatology in London, England, studying the biochemistry and cell biology of intervertebral discs. He was awarded his Ph.D. from University College, University of London in 1987. Aspects of his thesis work and subsequent studies on the intervertebral disc garnered two Volvo prizes for research in spine.
Dr. Johnstone pursued postdoctoral studies in articular cartilage biochemistry and cell biology at West Virginia University and the University of North Carolina at Chapel Hill, before moving to Case Western Reserve University, Cleveland, Ohio in 1993. He began work with mesenchymal stem cells at CWRU, pursuing basic and applied studies on chondrogenesis and cartilage repair and regeneration. This work has resulted in patents related to these studies. In 2002, Dr. Johnstone became an Associate Professor in the Department of Orthopaedics. Dr. Johnstone is now moving to OHSU as the Director of Research in the Department of Orthopaedics and Rehabilitation.
Research Overview
Current stem cell-related research projects
In vitro chondrogenesis of mesenchymal stem cells
Several funded studies are currently underway to investigate aspects of the chondrogenic differentiation of mesenchymal stem cells from various postnatal tissues; cell-cell and cell-matrix interactions are being examined, as well as secreted paracrine factors involved in this process. Intercellular and intracellular signaling pathways used by the stem cells during differentiation are of interest. These basic science studies are aimed at increasing our understanding of stem cell differentiation into chondrocytes. Findings from these studies are potentially useful for the translational research projects underway in the laboratory.
Tissue-engineering with stem cells
An NIH-funded study to assess the utility of tissue-engineered cartilage for meniscus repair and regeneration. Stem cells isolated from bone marrow are used to create cartilaginous tissue implants in a custom built hyaluronan/collagen scaffold using methods developed and patented by this laboratory. The implants are then tested in a large animal model of meniscus injury for their efficacy in repairing meniscal tears, and in a related aim, as meniscal replacements.
In a related study, novel UV-poymerizable scaffolds are under development for use with stem cells to create implants that are potentially injectable and can be polymerized in sites of cartilage and bone pathology, to create repair and/or regeneration of those tissues.
Selected references
Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp. Cell Res. (1998) 238: 265-272
Yoo JU, Barthel T, Nishimura K, Hering TM, Caplan AI, Goldberg VM, Johnstone B. The chondrogenic potential of human marrow-derived mesenchymal progenitor cells. J. Bone Joint Surg. (1998) 80-A:1745-1757
Yoo, J.U., Johnstone B. The role of osteochondral progenitor cells in fracture repair. Clin. Orthop. (1998) 355S:73-81
Angele P, Kujat R, Nerlich M, Yoo J, Goldberg V, Johnstone B. Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge. Tissue Eng. (1999) 5:545-553
Johnstone B, Yoo JU. Autologous mesenchymal progenitor cells in articular cartilage repair. Clin. Orthop. (1999) 367S:S156-S162
Nishimura K, Solchaga LA, Caplan AI, Yoo JU, Goldberg VM, Johnstone B. Chondroprogenitor cells of synovial tissue. Arth. Rheum. (1999) 42:2631-2637
Johnstone B, Yoo JU. In "Methods in Molecular Biology" (Series ed. J. Walker); "Developmental Biology Protocols" (eds. R. Tuan and C. Lo) The Humana Press, Inc. Bone marrow-derived mesenchymal progenitor cells. (2000) 137:313-5
Yoo JU, Mandell I, Angele, PA, Johnstone B. Chondroprogenitor cells and gene therapy. Clin Orthop. (2000) 379:S164-70
Hanada, K., Solchaga, L.A., Caplan, A.I., Hering, T.M., Goldberg, V.M., Yoo, J.U., Johnstone, B. BMP-2 induction and TGF-beta1 modulation of rat periosteal cell chondrogenesis. J. Cell. Biochem. (2001) 81:284-94
Angele P, Yoo J, Smith C, Mansour J, Jepsen, K J, Nerlich M, Johnstone B. Cyclic Hydrostatic Pressure Enhances the Chondrogenic Phenotype of Human Mesenchymal Progenitor Cells Differentiated In Vitro J.Orthop. Res. (2003) 21:451-457
Yoo J, Johnstone B. Tissue engineering of intervertebral disc. Orthopaedic Tissue Engineering: Basic Science and Clinical Practice, Marcel Dekker, NY (2004)
Hering TM, Kazmi NH, Huynh TD, Kollar J, Xu L, Hunyady AB, Johnstone B. Characterization and Chondrocyte Differentiation Stage-Specific Expression of KRAB Zinc-Finger Protein Gene ZNF470. Biochem Biophys Res Comm. (2004) In Press.
Johnstone B, Yoo J. Meniscus repair through tissue engineering. In: "Tissue Engineering in Musculoskeletal Clinical Practice " (eds. Sandell L, Grodzinsky A). American Academy of Orthopaedic Surgeons Symposium, Park Ridge (2004)
Johnstone B, Stewart M, Yoo J Cell sources for cartilage tissue engineering. In: "Culture of cells for tissue engineering" (eds. Freshney I, Vunjak-Novakovic G) Wiley, New York (In Press)