- 1999: Ph.D., Direct Ph.D. program, Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel. Supervisor: Prof. Benjamin
- Geiger.Thesis: The Structure and Function of Adhesion Signaling Complexes
- 1992: B.Sc., Magna Cum Laude, Biology, Faculty of Life Sciences, Hebrew University,Jerusalem, Israel
- Feb 2015-present: Professor, Biomedical Engineering Department, Technion, Israel Institute of Technology
- Sep 2011-July 2012: Visiting Professor, Wyss Institute for Biologically Inspired Engineering, Harvard University
- May 2009- present: Associate Professor, Biomedical Engineering Department, Technion, Israel Institute of Technology
- Oct. 2004- April 2009: Senior Lecturer, Biomedical Engineering Department, Technion, Israel Institute of Technology
- Summer 2006: Visiting Scientist, Prof. Robert Langer Lab, Chemical Engineering Department, MIT
- Sept. 2002- July 2004: Research Associate, Prof. Robert Langer Lab, Chemical Engineering Department, MIT.
- Sept. 2001- Aug 2002: Post Doctorate Associate, Prof. Robert Langer Lab, Chemical Engineering Department, MIT.
- Sept. 1999- Aug 2001: Post Doctorate fellow, EMBO Fellowship, Prof. Robert Langer Lab, Chemical & Biomedical Engineering Department, MIT.
Short Bio:Prof. Levenberg conducts interdisciplinary research on stem cells and tissue engineering. She did her PhD at the Weizmann institute on cell adhesion, and her post doctorate research on tissue engineering with Prof. Robert Langer at MIT. Her research showed that it is possible to create complex tissues including blood vessels in a laboratory and that these engineered tissue-constructs can integrate with the host when implanted. She is also developing micro bioreactors and nanoliter droplet devices for stem cell growth and manipulations. Levenberg received the Krill Prize for excellence in scientific research by the Wolf Foundation, and was named by Scientific American as a “Research Leader” in Tissue Engineering. Prof. Levenberg is currently the elected president of the Israel Stem Cell Society and serves as a member of the Israel National Bioethics Council.
- Shandalov Y, Egozi D, Freiman A, Dado-Rosenfeld D, Levenberg S A method for constructing vascularized muscle flap Methods 2015
- Lesman A, Gepstein L, Levenberg S Cell tri-culture for cardiac vascularization. Methods in Molecular Biology 2014
- Dado-Rosenfeld D, Tzchori I, Fine A, Chen-Konak L, Levenberg S Tensile forces applied on a cell-embedded three-dimensional scaffold can direct early differentiation of embryonic stem cells toward the mesoderm germ layer. Tissue Engineering Part A 2014
- Shemesh J, Ben Arye T, Avesar J, Kang JH, Fine A, Super M, Meller A, Ingber DE, Levenberg S Stationary nanoliter droplet array with a substrate of choice for single adherent/nonadherent cell incubation and analysis. PNAS 2014
- Shandalov Y, Egozi D, Koffler J, Dado-Rosenfeld D, Ben-Shimol D, Freiman A, Shor E, Kabala A, Levenberg S An engineered muscle flap for reconstruction of large soft tissue defects. PNAS 2014
- Avesar J, Ben Arye T, Levenberg S Frontier microfluidic techniques for short and long-term single cell analysis Lab on a Chip 2014
- Blinder YJ, Mooney DJ, Levenberg S Engineering approaches for inducing blood vessel formation Curr Opin Chem Eng 30:8(12) 2014
- Shamis Y, Silva EA, Hewitt K J, Brudno, Levenberg S, Mooney DJ, Garlick JA Fibroblasts Derived from Human Pluripotent Stem Cells Activate Angiogenic Responses In Vitro and In Vivo. PLOS One 2013
- Levenberg S Guest Editorial: New biomaterials for therapy. Israel Journal of Chemistry Israel Journal of Chemistry 9-10:607 2013
- Ne'eman N, Marbach D, Chen-Konak L, Kaufman-Francis K, Berkovich M, Levenberg S, Lotan N, Sivan S Multifactor, Sequentially Releasing Scaffolds for Tissue Engineering: Fabrication Using Solvent/Nonsolvent Sintering Technology. Israel Journal of Chemistry 9-10: 821-828 2013
- Dado D. and Levenberg S Induction of angiogenesis and vasculogenesis using biomaterials Israel Journal of Chemistry 9-10: 815-820 (2013)
- Rozitsky L, Fine A, Dado D, Nussbaum-Ben-Shaul S, Levenberg S, Yossifon G. Quantifying continuous-flow dielectrophoretic trapping of cells and micro-particles on micro-electrode array Biomed Microdevices 15(5):859-65 (2013)
- Blumenthal J, Cohen-Matsliah SI, Levenberg S Olfactory bulb-derived cells seeded on 3D scaffolds exhibit neurotrophic factor expression and pro-angiogenic properties Tissue Engineering Journal Part A 19:2284-91 (2013)
- Nseir N, Regev O, Kaully T, Blumenthal J, Levenberg S, Zussman E. Biodegradable scaffold fabricated of electrospun albumin fibers: mechanical and biological characterization Tissue Engineering Journal Part C 19(4):257-64. (2013)
- Kaufman-Francis K, Koffler J, Weinberg N, Dor Y, Levenberg S. Engineered vascular beds provide key signals to pancreatic hormone-producing cells. PLoS One 2012
- Tzezana R, Reznik S, Blumenthal J, Zussman E, Levenberg S. Regulation of stem cell differentiation by control of retinoic acid gradients in hydrospun 3D scaffold. Macromol Biosci. 2012
- Dado D, Sagi M, Levenberg S, Zemel A. Mechanical control of stem cell differentiation. Regen Med. 2012
- Zoldan J, Karagiannis ED, Lee CY, Anderson DG, Langer R, Levenberg S. The influence of scaffold elasticity on germ layer specification of human embryonic stem cells. Biomaterials. 2011
- Koffler J, Kaufman-Francis K, Shandalov Y, Egozi D, Pavlov DA, Landesberg A, Levenberg S. Improved vascular organization enhances functional integration of engineered skeletal muscle grafts. Proc Natl Acad Sci U S A. 2011
- Shemesh J, Nir A, Bransky A, Levenberg S. Coalescence-assisted generation of single nanoliter droplets with predefined composition. Lab on a Chip. 2011
- Lesman A, Koffler J, Atlas R, Blinder YJ, Kam Z, Levenberg S. Engineering vessel-like networks within multicellular fibrin-based constructs. Biomaterials. 2011
- Khoury M., Bransky A., Korin N., Chen Konak L., EnikolopovG., Tzchori I. and Levenberg S. A microfluidic traps system supporting prolonged culture of human embryonic stem cells aggregates. Biomedical Microdevices. 2010
- Shemesh J., Bransky A., Khoury M. and Levenberg S. Advanced microfluidic droplet manipulation based on piezoelectric actuation. Biomedical Microdevices. 2010
- Levenberg S., Ferreira L., Chen-Konack L., Kraehenbuehl T, and Langer R. Isolation, differentiation, and characterization of vascular cells derived from human embryonic stem cells. Nature Protocols. 2010
- Michael I., Walton D. and Levenberg S. Infantile Aphakic Glaucoma: A Proposed Etiologic Role of IL-4 and VEGF. Journal of Pediatric Ophthalmology. 2010
- Lesman A., Gepstein L. And Levenberg S. Vascularization shaping the heart. Ann N Y Acad Sci. 2010
- Lesman A., Blinder Y. and Levenberg S. Modeling of flow-induced shear-stress applied on 3D cellular scaffolds for vascular tissue-engineering applications. Biotechnology and Bioengineering. 2009
- Lumelsky Y., Lalush-Michael I., Levenberg S., and Silverstein M.S. Degradable, Porous, Emulsion-templated Polyacrylate. Journal of Polymer Science Part A: Polymer Chemistry 2009
- Lesman A., Habib M., Gepstein A., Arbel G., Levenberg S. and Gepstein L. Transplantation of Tissue-Engineered Human Vascularized Cardiac Muscle. Tissue Engineering Part A 2009
- Dado D, Levenberg S. Cell-scaffold mechanical interplay within engineered tissue. Semin Cell Dev Biol. 2009
- Kaully T, Kaufman-Francis K, Lesman A, Levenberg S. Vascularization--the conduit to viable engineered tissues. Tissue Eng Part B Rev. 2009
- Bransky A., Korin N., Khoury M. and Levenberg S. A Microfluidic Droplet Generator Based on a Piezoelectric Actuator. Lab on a chip. 2009
- Korin N, Bransky A, Khoury M, Dinnar U, Levenberg S. Design of Well and Groove Microchannel Bioreactors for Cell Culture. Biotechnology and Bioengineering Journal. 2009
- Levy-Mishali M., Zoldan J and Levenberg S. Effect of Scaffold Stiffness on Myoblast Differentiation. Tissue Engineering. Part A. 2009
- Korin N., Bransky A., Dinnar U. and Levenberg S. Periodic "Flow-Stop" Perfusion Microchannel Bioreactors for Mammalian and Human Embryonic Stem Cell Long-term Culture. Biomedical Microdevices. 2009
- Tzezana R. Zussman E., Levenberg S. A Layered Ultra-Porous Scaffold for Tissue Engineering, created via a Hydrospinning Method. Tissue Engineering. Part C. 2008
- Michael I., Shmoish M., Walton D and Levenberg S. Interactions Between Trabecular Meshwork Cells and Lens Epithelial Cells – A Possible Mechanism of Infantile Aphakic Glaucoma. IOVS (Invest Ophthalmol Vis Sci) 2008
- Bransky A., Korin N. and Levenberg S. Experimental and theoretical study of selective protein deposition using focused micro laminar flows. Biomedical Microdevices. 2008
- Lumelsky Y., Zoldan J., Levenberg S. and Silverstein M.S. Porous Polycaprolactone-Polystyrene Semi-interpenetrating Polymer Networks Synthesized within High Internal Phase Emulsions. Macromolecules 2008
- Korin N. and Levenberg S. Engineering human embryonic stem cell differentiation. Biotechnology and Genetic Engineering Reviews. 2007
- Korin N., Bransky A., Dinnar U. and Levenberg S. A Parametric Study of Human Fibroblasts Culture in a Microchannel Bioreactor. Lab on a Chip 2007
- Korin N., Bransky A., Dinnar U., and Levenberg S., A micro-well perfusion bioreactor for human embryonic stem cell Proc. microTAS 2007
- Levenberg S., Zoldan J., Bashevits Y. and Langer R. Endothelial potential of Human Embryonic Stem Cells. Blood 2007
- Caspi O. and Lesman A., Basevitch Y., Gepstein A., Arbel G., Habib M., Gepstein L., and Levenberg S. Tissue Engineering of Vascularized Cardiac Muscle from Human Embryonic Stem Cells. Circulation Research. 2007
- Korin N., Branski A., Dinnar U. and Levenberg S. The culture of human embryonic stem cells in microchannel perfusion bioreactors. Proc. SPIE Biomedical Applications of Micro- and Nanoengineering III 2006
- Levenberg S. Endothelial tissue engineering. Journal of Vascular Research. 42 suppII: 7 (2005)
- Levenberg, S. Engineering blood vessels from stem cells: recent advances and applications. Current opinion in Biotechnology. 2005
- Levenberg, S., Rouwkema, J., Macdonald, M., Gerfein, E., Kohane, D., Darland D., Marini, R., van Blitterswijk, C.A., Mulligan, R., D’Amore, P. and Langer, R. Engineering Vascularized Skeletal Muscle Tissue. Nature Biotechnology. 2005 Cited as a Landmark paper is Nature Biotechnology News and Views.
- Levenberg, S., Burdick, J.A., Kraehenbuehl, T., and Langer, R. Neurotrophin Induced Differentiation of Human Embryonic Stem Cells on Three-Dimensional Polymeric Scaffolds. Tissue Engineering. 2005
- Levenberg S, Langer R. Advances in tissue engineering. Curr Top Dev Biol. 2004
- Anderson, D.G., Levenberg, S., and Langer, R. Nanoliter-scale synthesis of arrayed biomaterials and its application to human embryonic stem cells. Nature Biotechnology. 2004
- Khademhosseini, A., Suh, K.Y., Yang, J.M., Eng, G., Yeh, J., Levenberg, S. and Langer, R. Layer-by-layer Deposition of Hyaluronic Acid and Poly-L-lysine for Patterned Cell Co-Cultures. Biomaterials. 2004
- Levenberg, S., Huang, N., Erin, L., Rogers, A., Itskovitz-Eldor, J. and Langer, R. Differentiation of Human Embryonic stem cells on Three Dimensional Polymer Scaffolds. PNAS. 2003
- Levenberg, S., Golub, J. S., Amit, M., Itskovitz-Eldor, J. and Langer, R. Endothelial Cells Derived From Human Embryonic Stem Cells. PNAS 2002 Cited in the list of 20 most cited papers on hESC from 1998-2004
- Levenberg, S., Yarden, A., Kam, Z. and Geiger, B. p27 is Involved in N-cadherin-mediated Contact Inhibition of Growth and S-phase Entry. Oncogene. 18:869-876 (1999)
- Levenberg, S., Sadot, E., Goichberg, P. and Geiger, B. Cadherin - Mediated Transmembrane Interactions. Cell adhesion and Communication. 6:161-170 (1998)
- Kats, B.Z., Levenberg, S., Yamada, K.M., and Geiger, B. Modulation of Cell-Cell Adherence Junctions by Surface Clustering of the N-Cadherin Cytoplasmic Tail. Experimental Cell Research. 243:415-424 (1998)
- Levenberg, S., Yamada, Katz BZ, Yamada KM, Geiger B. Long-Range and Selective Autoregulation of Cell-Cell or Cell Matrix Adhesions by Cadherin or Integrin Ligands. J. Cell Science. 111:347-357 (1998)
- Simcha, I., Geiger, B., Yehuda-Levenberg, S., Salomon, D., and Ben-Ze'ev, A. Suppression of Tumorigenicity by Plakoglobin: An Augmenting Effect of N-cadherin. J. Cell. Biolog. 1996
- Geiger, B., Yehuda-Levenberg, S. and Barshadsky, A. Molecular Interactions In The Submembrane Plaque of Cell-Cell and Cell-Matrix Adhesions. Acta Anat. 1995
- Zoldan, J. and Levenberg, S. Culturing and Differentiation of hES cells on three dimensional scaffolds. Methods in Molecular Biology - New Stem Cell Techniques. Humana Press. In Press
- Soukup C., Levenberg S. and Cleaver O. In vitro differentiation of endothelial cells from human embryonic stem cells. Human Embryonic Stem Cells: A Practical Approach. Editors: Stephen Sullivan, Chad A Cowan, Kevin Eggan. John Wiley & Sons. NJ. 13, 229-248 (2007)
- Malda, J., Baaijens, F., Levenberg, S., Radisic, M., Svalander, P., Woodfield, T. and Vunjak-Novakovic, G. Cell nutrition. In Textbook on tissue engineering. Editors: van Blittersvijk, C., Lindahl, A., Thomsen, P., Williams, D., Hubbell, J. and Cancellah, R. Academic Press. Amsterdam. 327-362. (2008)
- J. Zoldan and S. Levenberg Engineering Three-Dimensional Tissue Structures Using Stem Cells. Methods in Enzymology: Stem Cells Volume. Edited by R. Lanza and I. Kilmanskaya, Elsevier. 381-3420 (2006)
- Levenberg, S., Khademhosseini, A., Fuller, J. and Langer, R. Methods of Human Embryonic Stem Cell Culture. In Culture of Cells for Tissue Engineering. Editors: Ian Freshney and Gordana Vunjak-Novakovic. John Wiley & Sons. NJ. 61-83. 2006
- Levenberg, S., Khademhosseini, A. and Langer, R. Embryonic Stem Cells in Tissue Engineering. In Handbook of Embryonic Stem Cells. Editors: Robert Lanza, Doug Melton, James Thomson, John Gearhart, Brigid Hogan, Ron McKay, Roger Pedersen and Mike West. Academic Press. Boston. 737-764. 2006
- Levenberg, S., Huang, N. and Langer, R. Derivation of Endothelial Cells from Human ES Cells. In Human Pluripotent Stem Cells Editors: Jon S. Odorico, Roger A. Pedersen, and Su-Chun Zhang
Main Research Interests
Research interests: Vascularization of engineered tissues. Stem cell differntiation on 3D scaffolds.Controling stem cell microenvironments
Research TopicsThe rapidly increasing demand for organ and tissue transplantation has promoted tissue engineering and stem cell research as promising approaches. Tissue engineering combines cells, growth factors and 3D scaffolds for repair and regeneration of biological tissues. To advance tissue engineering research, scaffold properties must be optimized for a given application and cell type. This includes chemical and mechanical properties, shape, and structure and degradation rate. In addition co-culture approaches are required to allow organization of complex tissue structures. Endothelial cell co-cultures are important for inducing vascularization of engineered tissues. Our experiments in engineered skeletal and cardiac muscle tissue indicate that endothelial cells promoted differentiation and organization of the co-cultured myoblasts. Endothelial 3D tubular networkswere formed within the tissue and shown to promote vascularization upon implantation. Our recent results using pancreatic islets co-cultures further support the inductive effect of endothelial vessels on islets survival in vitro and in vivo. Given the attractive potential of human embryonic stem cells in tissue regeneration we evaluate the ability to differentiate the cells and induce their 3D organization toward formation of complex tissues. Porous biodegradable polymer scaffolds are ideal system for exploring 3D tissue formation, providing support for the cells that can be modulated by modifying cell adhesion sites. Following degradation, the polymers can promote further growth of cells and provide space for remodeling of tissue structures. In addition, degradation of the scaffolds can be used as a tool for localized and controlled growth factor supplementation. Biodegradable, growth factor-eluting nano-fibers are also used to study embryonic stem cells process in 3D models. Differentiation of the cells is further studied in micro perfusion system to allow the precise localization of a growth factor, both temporally and spatially using laminar flows. The technique can provide a tool to investigate cell-cell signaling between adjacent embryonic stem cells by maintaining a constant gradient of growth factors in the surrounding culture medium. Understanding stem cells differentiation and 3D cellular communications can lead to advances in cell therapy and tissue engineering and facilitate organ and tissue regeneration.
Vascularization of engineered tissue constructsThe uniqueness of this approach (developed by Levenberg et al and first published in Nature Biotechnology 2005) is to induce vessel network assembly within 3D tissue constructs in vitro by multicellular culturing of endothelial cells (ECs) and vascular mural cells with cells specific to the tissue of interest. Levenberg has shown that such in vitro prevascularization of engineered tissue can promote its survival and vascularization upon implantation. The ongoing projects in the lab focuses on characterizing the mechanisms of in vitro vascularization and vessel-network formation in multi-cellular tissue constructs by using defined biomaterials and mechanical stimulation designed to mimic in vivo settings. In addition, this study aims to elucidate the signaling effects and in vivo integration process of engineered vessel network with host vasculature. Several in vivo models are being used for real-time investigation of the vascularization and integration of engineered vascularized constructs. In addition, new strategies are being developed for fabrication of engineering vascularized flaps. Additional focus is placed on the effects of interstitial flow and tensile forces on the self-assembly of endothelial cells into vascular networks in vitro. The effects are being characterized and quantified using a combination of bioreactor setups, computational modeling, 3D image analysis and gene expression studies. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501.
Engineering vascularized cardiac tissueOur aim is to create in vitro pre-vascularized cardiac tissue using a multi-cellular seeding strategy. This strategy involves co-culturing 3 types of cells (i.e. cardiomyocytes, endothelial cells and fibroblasts) within a nano-patterned scaffold.Cardiac tissue engineering aims to create functional tissue constructs that can re-establish the structure and function of injured myocardium. The cellular organization of the heart consists primarily of cardiomyocytes, fibroblasts, vascular smooth muscle cells, and endothelial cells. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501. Flow-induced vascularization in engineered tissue One of today’s major challenges in engineering complex three-dimensional functional tissues is proper vascularization – cells need to be in close proximity (~100µm) to blood vessels in order to survive. The research focuses on the effects of interstitial flow on the self assembly of endothelial cells into vascular networks in vitro. Using a combination of perfusion-bioreactor design, computational fluid dynamics (CFD) modeling, fluorescence microscopy image analysis and gene expression analysis, we are working to characterize and quantify these effects. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501. Engineering skeletal muscle tissue- as graft and flaps for reconstruction of abdominal wall tissue This study offers novel reconstruction techniques in the form of an alternative biomaterial implantation (vascularized engineered skeletal muscle tissue), offering the possibility to repair a full-thickness defect of the abdominal wall without the need to transfer tissue (autologous muscle free flap) from another site and minimal postoperative scarification. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501. Engineering a vascular niche to support pancreatic islet survival and function and to improve islet transplantation efficacy The working hypothesis of this study is that non-nutritional, EC-generated signals may be paramount to in vitro culturing of islets for the purpose of boosting early graft infusion survival prospects. The study aims to reconstruct pancreatic tissue consisting of islets or beta cell progenitors enriched with a vascular milieu that both supports and promotes graft integration and function. Particular focus is being placed on understanding the inductive signals and characterizing the resulting 3D vascular networks and on evaluating its capacity to treat a Type 1 diabetes. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501.
spinal cord injury regenerationSpinal cord injury is devastating to both patients and their families. Among the strategies being investigated to promote regeneration is the transplantation of stem cells. We aims to exploit the supportive properties of stem cells and other neuronal cells in combination with endothelial cells and a biodegradable scaffold, as a strategy to preserve spared neural tissue, and promote a more hospitable environment for vasculogenesis and neural regeneration.
Cell mechanics in 3D constructsIn this project we investigate the mechanical interplay between cells and scaffold within 3D engineered constructs. We examine the influence of cells seeded within scaffold via measurements of contractile forces and the influence of mechanical constraints of the scaffold on cell behavior mainly focusing on embryonic stem cells differentiation. We combine different methods such as tissue engineering techniques, bioreactors (and new designs), gene analysis and finite elements modeling. Droplet Based Microfluidics We have developed innovative methods to create and manipulate nanoliter volume droplets in microfluidic channels. We were able to achieve on demand generation of nanoliter droplets, purely hydrodynamic droplet sorting, and accurate droplet composition control. Our latest work brought stationary nanoliter droplet arrays on a substrate of choice for the culture and analysis of single adherent and non-adherent cells. We are currently using these modules to answer biological questions by implementing single cell assays.
The Rina & Avner Schneur Type II Diabetes centerThe Rina & Avner Schneur Type II Diabetes center lead by Prof. Levenberg, brings together top researchers from the faculty of Biomedical engineering and the Faculty of Medicine at the Technion-Israel Institute of Technology to seek for a cure to type II diabetes. Type II Diabetes (DM2) is one of the most important public health challenges requiring a cure rather than preventive treatment. The current project (In collaboration with Prof Eddy Karnieli) focuses on the development of a new cure for this important disease in the form of transplantation of engineered tissue, which will provide a useful tool to reach better systemic glucose homeostasis in DM2.