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How the landscape defines cell character

The environment has an impact - not only on human beings but also on their cells. Researchers involved in the EU-sponsored CellPROM project intend to exploit this phenomenon by constructing molecular environments in which cells precisely develop the specific traits required for cell therapy and biotechnological applications.

You may not have seen an old friend for years, and yet you immediately recognize each other while passing by on the street. It might seem natural, but in fact it is astonishing, as Professor Günter Fuhr of the Fraunhofer Institute for Biomedical Engineering IBMT in St. Ingbert explains: "Skin cells only survive for a couple of months before dying and being replaced by new cells. When you run into your old friend after many years, there is not a single cell in his face that was there when you used to know him. And yet you still recognize each other. The basic overall pattern is reproduced to an extraordinary extent." This precise reproduction of cells cannot be satisfactorily explained in terms of genetics. "If genes alone were responsible, you would not be able to recognize your friend after even just a few months: Each cell division produces mutations, and so the transmission of information is never entirely exact. But interaction between the cellular surfaces, nonetheless, influences the result, ensuring that cells are reproduced into an almost identical pattern", explains Professor Günter Fuhr, director of the IBMT and coordinator of CellPROM. In collaboration with 27 research teams from all over Europe, Fraunhofer scientists intend to spend the next four years investigating ways of utilizing surface interactions to deliberately manipulate the characteristics of cells. The surface interaction between cells not only regulates their shape but also their function. If, for example, a still undifferentiated stem cell floats past a specific type of bone marrow cell, a macromolecular binding process takes place between their surfaces. This type of reaction determines whether the stem cell will develop into a red or a white blood cell, an thus whether it will in the future be transporting oxygen through blood vessels or become part of the body's immune system and ingest viruses or bacteria. "It is the surface that determines what type of cell it will become, and only thereafter, the corresponding genetic program will be activated," resumes Fuhr. In theory, it ought to be possible to exploit such molecular interactions to harvest cells for therapeutic use, for instance to support the immune defense system, or to combat viral infections, or to provide a substitute for blood cells destroyed by cancer. Conventional cell therapy employs adult stem cells, typically extracted from the patient's bone marrow, which are multiplied in the laboratory and re-injected into the body. But cells cultivated in laboratory dishes made of glass are deprived of contact with biologically stimulating surfaces. Consequently, they are not preprogrammed to take on such specific tasks as fighting cancer or transporting oxygen. The researchers working on the CellPROM project intend to develop means of populating artificial surfaces with macromolecules, thus creating "nanomolecular environments" that could be used to manipulate cell development. The name "CellPROM" derives from "cell" and "EPROM" - an "erasable programmable read-only memory" is a type of reprogrammable computer chip. "Our vision is to be able to differentiate individual cells", relates Fuhr. "During the project, we hope to develop a modular system of instruments that emulate the processes taking place in the human body, where stem cells differentiate into 220 different types of cells, depending on requirements. If we manage to successfully mimic these processes, we will be able to produce cells specifically designed to treat cancer, immunodeficiency and autoimmune diseases, or hemophilia. The problem of rejection by the immune system is avoided, because cell therapy only uses stem cells taken from and reinjected into the patient's own body." Research groups in Germany, Switzerland, Sweden, Spain, Portugal, Belgium, Austria, France, Italy, Lithuania, Slovenia and Israel are working on the technical details. The Institute for New Materials in Saarbrücken, for example, is looking into suitable nanoparticles, while the Fraunhofer Institute for Reliability and Microintegration IZM in Berlin is conducting research into various nanostructures and ways of constructing sterile microsystems. The Institut Pasteur in Paris will supply a range of cell cultures for the early experimental phase, and the research departments of numerous private companies are working on the development of suitable devices and automated manufacturing systems. The various development initiatives converge at the IBMT. Professor Fuhr compares the project with the construction of a space satellite: "The modules are developed in different locations and only at the last moment assembled in one place". In four years' time, the main modules of an automated CellPROM machine will be tested at the IBMT. The entire system hardware, including monitors, microscopes and process-monitoring computers, will fill a whole special laboratory, while the actual cell programming will take place on a much smaller scale. The stem cells are fed into the system through narrow tubes in which they are confronted with defined macromolecular environments. In the course of just a few hours, through interaction with their nano-environment, they develop into specialized cells that are ideally primed to assume specific functions. At this stage, the prototype will still not be capable of supplying cells for therapeutic use, and work on developing the CellPROM machine to commercial maturity will not begin until the project has been completed. Then, it will be possible to start clinical trials.,For further information: ,Prof. Gunter Fuhr,Phone +49 (0) 68 94 / 9 80-1 00 ,Fax +49 (0) 68 94 / 9 80-1 10 Fraunhofer-Institut fur Biomedizinische Technik IBMT,Ensheimer Stra?e 48,66386 St. Ingbert, Germany,