报告题目一：Additive Manufacturing of Tissues and Organs

报告题目二：Tumor Engineering 

报告人：Prof.  Dietmar W. Hutmacher

时 间：5月29日（周二）下午1:00
地 点：文史楼205 
主持人：葛子钢（特聘研究员）

报告一内容摘要：
    Additive manufacturing techniques offer the potential to fabricate organised tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations of cells along multiple axes with high geometric complexity in combination with different biomaterials can be generated. The level of control offered by these computer-controlled technologies to design and fabricate tissues will accelerate our understanding of the governing factors of tissue formation and function. Moreover, it will provide a valuable tool to study the effect of anatomy on graft performance. In this review, we discuss the rationale for engineering tissues and organs by combining computer-aided design with additive manufacturing technologies that encompass the simultaneous deposition of cells and materials.

报告二内容摘要：
    It is a sine qua non that cells in a living organism exist within a three-dimensional (3D) polymeric sugary protein environment commonly called the extracellular matrix (ECM). The ECM serves as a functional scaffold that regulates many cellular responses as well as maintaining the correct tissue architecture.  In fact, the ECM plays a pivotal role in development, homeostatic maintenance, tissue regeneration and it responds to many pathological situations such as wound healing, inflammation, fibrosis and cancer.  In addition the ECM serves as a rich reservoir of nutrients, hormones and other factors.  It also plays an important role in removal of waste products and it even coordinates mechanical as well as biochemical cues thought all these functions.  ECMs vary in different organs and locations.  For example the epithelial ECM better known as basal lamina or basement membrane is a laminin based rug-like and rather impermeable layer that serves for epithelial cells to attach while it also separates between epithelium and mesenchyme.  In comparison, the mesenchymal ECM is a highly pours mesh like matrix where resident cells intercalate within it as opposed to resting upon.  .
    However, the vast majority of in vitro studies, particularly in the cancer field, fail to mimic the particular physiologically relevant 3D environments, and instead many are still conducted under classic two dimensions, in Petri dishes, multi-well plates or glass slides that have been coated with various ECM proteins, such as collagen, laminin or fibronectin.  It is therefore understandable that there are noteworthy limitations associated with two-dimensional (2D) cell culture experiments, such as lack of reproduction of physiological patterns of cell adherence, cytoskeletal organization, migration, signal transduction, morphogenesis, proliferation, differentiation and response to therapeutic stimuli (among others).
    Needless to say, the vast majority of in vitro tumor biology studies are even now performed using monolayer cultures, and thus there is a big risk of misinterpretation of the data that could lead to inaccurate generation of hypotheses.  Fortunately, a growing number of cancer researchers, aware of the limitations of conventional 2D monolayer cell cultures, are moving towards the use of more physiologically relevant 3D cell culture systems as they begin to understand that the microenvironmental cues found in the tumor-associated stroma in general and the tumoral ECM in particular are equally as important as the cancer cell itself.
    While this idea was well articulated by Theodor Langhans in 1879 and Paget presented his famous “seed and soil” theory in 1889 it took almost a century for Mintz and colleagues to report that normal host environments could restrict the neoplastic growth of teratocarcinoma cells microinjected into blastocysts.  In fact, it wasn’t until 1985 that Miller and colleagues showed that tumor cells exhibit greater drug resistance when grown as multicellular spheroids in a collagen gel compared to when grown in a monolayer.  Perhaps best known for her pioneering work, Mina Bissell introduced the use of in vivo mimetic 3D culture systems to model the molecular mechanisms of breast tumorigenesis and invasion by using the mammary gland as a model system.  Her group and others have shown that epithelial tumor cells are prompted to shape, polarity and additional changes in a microenvironmental dependent manner using a naturally derived laminin based basement membrane type of ECM known as Matrigel.
    Over the last two decades, we have seen that 3D cultures using tissue engineered scaffolds, as well as naturally harvested and cell derived matrices have played key roles in the advancement of basic research, tissue engineering and regenerative medicine.  Although the field of tissue engineering has mainly focused to date on direct clinical applications in regenerative medicine, tissue engineering offers a potentially powerful tool box for other areas in the biomedical sciences.  Among these are the establishments of more physiological in vitro and/or in vivo models that can be used to study disease pathogenesis, such as cancer or to develop molecular therapeutics, as well as to screen for toxic effects of drugs on human tissues etc. Based on the background penned out above the talk aims to present on the recent developments of engineering of tumor microenvironments