The 21st Century COE Program
Center of Excellence for Research and Education on Complex Functional Mechanical Systems

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English

International Workshop on
Mechanics of Complex Biological Systems in Tissue and Cells

開催概要

プログラム (13:30-17:00)

講演要旨

Signalling between Cartilage and Endothelial Cells in a Tissue Engineered Model

Juan M. Taboas (NIH & NIST), Rocky S. Tuan (NIH, NIAM), Steven D. Hudson (NIST)

Signaling between cartilage and vasculature tissue may mediate limb development, fracture healing, and skeletal disease. In arthritis, altered mechanical loads and inflammatory cytokines modify the tissue homeostasis. We have developed a tissue engineered model to probe the interaction between cartilage and the vasculature in vitro. A novel micro-fluidic bioreactor and a hydrostatic pressure loading device have been constructed to culture and stimulate 3D constructs. Cell morphology, proliferation, and gene expression have been investigated in response to chondrocyte and human microvascular endothelial cells co-culture and to stimulation with dynamic hydrostatic compression, growth factors and cytokines implicated in arthritis. The results demonstrate that chondrocytes endogenously secrete angiogenic factors that enhance endothelial cell proliferation/viability and that endothelial cells secrete factors that may increase chondrocyte matrix turnover and decrease chondrocyte production of angiogenic factors. This study is relevant to the clinical success of tissue engineered cartilage and demonstrates the utility of engineered models to investigate complex biologic systems.

This work is supported by the NIAMS Intramural Research Program and a National Research Council fellowship to JMT.

Visualizing Molecular Signalings in Live Cells

Yingxiao Wang (Dept of Bioengineering, Univ. of Illinois at Urbana-Champaign)

Tyrosine kinases have been shown to play critical roles in a variety of cellular processes, including cell motility/migration, mechanotranduction, and cancer development. Based on fluorescent resonance energy transfer (FRET), we have developed and characterized a genetically encoded single-molecule Src reporter, which enables the imaging and quantification of tempo-spatial activation of Src in live cells. We introduced a local mechanical stimulation by applying laser-tweezer-traction on fibronectin-coated beads adhered to the cells. Using the Src reporter, we observed a rapid Src activation and a slower directional wave propagation of Src activation along the plasma membrane. This Src reporter was also applied to visualize the dynamic Src activation at subcellular levels in a variety of cellular processes and functions, including the interplay between cell-cell and cell-ECM adhesions, the epherin-induced growth cone collapse of hippocampal neuronal cells, and the cancer development. With a similar strategy, we have developed a new reporter for focal adhesion kinase (FAK). Pilot studies revealed that there is a hot zone with high FAK activities at the base of lamellipodium in spreading cells, suggesting an important role of focal adhesion turnover in cell motility. In summary, our novel reporters have made it possible to monitor key signaling transduction cascades in live cells with tempo-spatial characterization and to detect cancerous cells with high fidelity.

Novel Bioinspired Materials to Control Cell Function and Tissue Regeneration

Eben Alsberg (Case Western Reserve University)

Musculoskeletal injuries are a major source of pain and disability throughout the world, and millions of operations involving bone and cartilage repair are performed annually. Tissue engineering, which is the regeneration of tissues to replace those damaged or lost as a result of disease, trauma, or congenital abnormalities, has the potential for improved restoration of functional tissues compared to current therapies. One promising tissue engineering approach involves the transplantation of isolated cells on a biodegradable delivery vehicle. The ultimate goal of this strategy is to create a functional biological replacement tissue without permanent remnants of foreign constituents. Development of innovative ways to present specific biochemical and physical signals to control cell behavior may be necessary to guide the process of tissue regeneration. This presentation will describe how cellular behavior may be positively modulated when engineering tissue by regulating cell-biomaterial interactions, controlling polymer degradation, delivering soluble bioactive signals, and providing contact guidance cues.