- Cell-extracellular matrix interactions
- Tissue engineering of skeletal and cardiac muscle
Dr. Louis Terracio is Associate Dean for Research, Professor in the Department of Basic Science and Craniofacial Biology and Professor of Pediatrics at the School of Medicine. Dr. Terracio has been PI or Co-PI on over $15 million in NIH grants. He currently has a grant from NIDCR/NIH to study Tissue Engineering of Skeletal Muscle. He has extensive teaching experience in both biomedical and PhD graduate programs. He has been on over 25 graduate student committees and has mentored scores of students ranging from high school through Surgery and Cardiology Fellows. Dr. Terracio’s research interests center on Cell-Extracellular Matrix (ECM) interaction during development and in disease. In particular his lab investigates the role of integrins in the formation of normal muscle. An intact ECM-Integrin-Cytoskeletal complex appears to be essential for normal muscle orientation and pattern formation. His lab uses recombinant adenovirus to manipulate the integrins present on the cell surface of myocytes in culture and determine the role of specific integrins on myofibrillogenesis and overall myocyte phenotype. Dr. Terracio’s lab also studies the role of stretch as a potential morphogenic signal using a tissue culture model of aligned myocytes. His lab has demonstrated that thin aligned gels of collagen result in cultured myocytes taking on an elongated rod shape similar to in vivo. This system allows these scientists to investigate the effects of stretch on myocytes in either the long axis of the cell or across the short axis, where the ECM-Integrin-Cytoskeletal complex is most abundant. Data from this model coupled with data from a low shear culture environment on the Space Shuttle has led Dr. Terracio to focus his current research on tissue engineering cardiac and skeletal muscle.
His lab has developed a cardiac patch that has many of the features of intact cardiac muscle. Although this patch will not have utility in replacing cardiac muscle in vivo as was originally hoped, the cardiac patch has proven to have utility as a model system for the study of cardiac muscle in vitro. A movie of the tissue engineered cardiac muscle can be seen at http://www.nyu.edu/dental/faculty/directory/terraciocardiac.mov. What you will see are four different examples of cardiac patches spontaneously beating in culture. Each of these patches is about 4 weeks old and is constructed using our specially fabricated collagen substrates seeded with neonatal rat cardiac myocytes. The largest is about 18 x 95 x 1 mm and rotates in the culture dish as it contracts. We have maintained similar patches in culture for over 10 weeks. The Terracio lab is currently working with Dr. Kathleen Kinnally to study the bystander effect in apoptosis after myocardial infarction using cryoablation in this system.
Dr. Terracio’s lab is one of the first to tissue engineer a skeletal muscle construct that has structure and function similar to intact muscle. The muscle constructs tetanize and have length tension curves that are nearly identical to in vivo skeletal muscle. The magnitude of the force generated is very small since due to the small cross sectional area of the constructs. The lab is currently transplanting the constructs into animals to determine the feasibility of this system to replace lost skeletal muscle.
Yan W, George S, Fotadar U, Kamer A, Yost MJ, Price RL, Haggart CR, Holmes JW, Terracio L. 2007. Tissue engineering of skeletal muscle. Tissue Eng, 13: 2781-2790.
Fann SA, Terracio L, Yan W, Franchini JL, Yost MJ. 2006. A model of tissue-engineered ventral hernia repair. J Invest Surg. 19: 193-205.
Mironov V, Kasyanov VA, Yost MJ, Visconti R, Twal W, Trusk T, Wen X, Ozolanta I, Kadishs A, Prestwich GD, Terracio L, Markwald RR. 2006. Cardiovascular tissue engineering I. Perfusion bioreactors: a review. J Long Term Eff Med Implants 16: 111-30. Review.
Fotadar U, Zaveloff P, Terracio L: 2005. Growth of Escherichia coli at elevated temperatures. J Basic Microbiol 45: 403-404.
Terracio L, W. Yan, R. Price, M. Yost, D. Simpson. 2004. Tissue Engineering of Cardiac and Skeletal Muscle: Lessons Learned from Micropatterned Collagen and Microgravity. Gravitational and Space Biology Bulletin. 17: 67-74.
Young HE, C Duplaa, M Romero-Ramos, M-F Chesselet, P Vourc’h, MJ Yost, K Ericson, L Terracio, … and AC. Black Jr. 2004. Clonogenic Analysis Reveals Reserve Stem Cells in Postnatal Mammals. II. Pluripotent Epiblastic-Like Stem Cells. The Anatomical Record. Part A 277A:178-203.
Young HE, C Duplaa, M Romero-Ramos, M-F Chesselet, P Vourc’h, MJ Yost, K Ericson, L Terracio, … and AC Black Jr. 2004. Adult Reserve Stem Cells and Their Potential for Tissue Engineering. Cell Biochemistry Biophysics, 40: 1-80.
Yost MJ, CF Baicu, CE Stonerock, RL Goodwin, RL Price, JM Davis, H Evans, PD Watson, CM Gore, J Sweet , L Creech, MR Zile, and L Terracio. 2004. A Novel Tubular Scaffold for Cardiovascular Tissue Engineering. Tissue Engineering. 10: 273-84.
Price RL. ST Haley, TA Bullard, EC Goldsmith, DG Simpson, TE Thielen, MJ Yost, LTerracio. 2003. Effects of platelet-derived growth factor-AA and -BB on embryonic cardiac development. Anatomical Record. 272A(1):424-33.
Burgess ML, L Terracio, T Hirozane, TK Borg. 2002. Differential integrin expression by cardiac fibroblasts from hypertensive and exercise-trained rat hearts. J. Cardiovas Path 11(2):78-87.
Price RL, TE Thielen, TK Borg, L Terracio. 2001. Cardiac defects associated with the absence of the platelet-derived growth factor alpha receptor in the Patch mouse. Microscopy and Microanalysis. 7:56-65.
Yost, M.J., RL Price, DG Simpson, and L Terracio. 2001. Artifical Myocardium: Design Principles and Substratum. Microscopy and Microanalysis. 7 (suppl 2): pp. 138-139.
Yost, MJ, D Simpson, K Wrona, S Ridley, HJ Ploehn, TK Borg and L Terracio. Dec 2000. Design and Construction of a Uniaxial Cell Stretcher. American Journal of Physiology, Heart and Circulatory Physiology., 279:H3124-H3130.
Simpson DG, M Majeski, TK Borg and L Terracio. 1999. Regulation of Cardiac Myocyte Protein Turnover and Myofibrillar Structure: In Vitro by Specific Directions of Stretch. Circulation Research 85(10):1-11.
Simpson DG, TA Reaves, D-T Shih, W Burgess, TK Borg and L Terracio. 1998. Cardiac Integrins: The Ties That Bind. Cardiovasc. Path. 3:135-143.
Price RL, W Carver, DG Simpson, L Fu, J Zhao, TK Borg and L Terracio. 1998. The Effects of Angiotensin II and Specific Angiotensin Receptor Blockers on Embryonic Cardiac Development. Dev. Biology. 192:572-584.
Sharp WW, DG Simpson, TK Borg, AM Samarel and L Terracio. 1997. Contractile activity and external mechanical tension affect focal adhesion formation by cultured neonatal rat cardiac myocytes. Am. J. Physiol. 273(42):H546 - 556.
Nakagawa M, RL Price, C Chintanawonges, DG Simpson, MJ Horacek, TK Borg and L Terracio. 1997. Analysis of heart development in cultured rat embryos. J. Mol. Cell. Cardiol. 29:369-379.