How the landscape defines cell character
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,"
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
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.
Prof. Günter Fuhr
Phone +49 (0) 68 94 / 9 80-1 00
Fax +49 (0) 68 94 / 9 80-1 10
Fraunhofer-Institut für Biomedizinische Technik
Ensheimer Straße 48
66386 St. Ingbert, Germany