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Blood - a key resource for regenerative medicine

Prof. Dr. Hinnak Northoff, Medical Director of the ZKT (Photo: private)

Prof. Dr. Hinnak Northoff, Medical Director of the ZKT (Photo: private)

Transfusion medicine plays a huge part at the University Hospital of Tübingen (UKT) – a special institute was established with a specific research focus on the application and use of blood in regenerative medicine.

Blood is quite a peculiar kind of juice – probably even more so today than when Goethe immortalised this sentence in "Faust". Blood donations and transfusion save lives and have become an indispensable part of modern medicine. Research is equally reliant on this elixir of life – for example, in regenerative medicine, blood serves as a source for stem cells and blood serum is used as a medium for cell culture.

Prof. Dr. Hinnak Northoff is the Medical Director of the ZKT (Centre for Clinical Transfusion Medicine gGmbH), a 75% subsidiary of the DRK (German Red Cross) and the IKET (Institute of Clinical and Experimental Transfusion Medicine), another UKT institute. Northoff refers to the central role of transfusion medicine for regenerative projects at the UKT and its general importance in clinical application and research: "Apart from the supply of "classical" blood products like erythrocyte, thrombocyte concentrates and plasma, as a blood bank we cater for the supply of serum and buffy coat, which is a concentrate consisting of leukocytes and thrombocytes. In addition, we are an important supplier of GMP technology for the nearby institutes and hospitals." The ZKT/IKET is equipped with cleanrooms in which work is carried out in compliance with the high international GMP (good manufacturing practice) standards.

ZKT/IKET is aiming to expand GMP area

The availability of the required laboratories and the ZKT/IKET’s GMP expertise, make the Department of Transfusion Medicine in Tübingen an important cooperation partner. The number of inquiries is continually increasing to the extent that the institute is concerned that it will soon reach capacity. "It is important for future operations that we can further expand the GMP facilities and establish a central GMP unit at the University Hospital. We hope the state of Baden-Württemberg will give its financial support to enable us to make these important investments for the future," said Northoff.

Northoff and his team started working in compliance with GMP standards quite a while ago. This foresight has now led to Northoff and his team receiving the first ever authorisation in Germany to produce pancreatic island cells. These cells are used in patients who cannot undergo transplantation using established methods. "Island cells need to be produced in GMP laboratories. In order to do this, we have invested a lot of time, money and equipment," said Northoff. Dr. Marc Waidmann heads the team at the ZKT, working closely in cooperation with Prof. Dr. Alfred Königsrainer’s team at the University Hospital of General, Visceral and Transplantation Surgery. The Tübingen surgeons are the first to benefit from the pancreas cells prepared in vitroi. However, other transplantation centres can also obtain cell material from the ZKT.

Blood serum for regenerative therapies

Blood serum "made in Tübingen" is also very popular, for example, in the regenerative cell therapies that have themselves become increasingly popular. The ZKT has also recently received an authorisation to produce blood serum, which is required for the preparation of media in which cells are cultured for subsequent transplant. "Pooled sera consisting of sera from different patients with the same blood group are particularly popular. They are used as part of individual treatment regimens," said Northoff. The sera are produced under GMP conditions from full-blood donations, and are placed in quarantine like human blood plasma, before being supplied to the UKT and other hospitals.

Stem cell research is being extended

For one and a half years now, Northoff and his team have been involved in ambitious research projects involving mesenchymal stem cells (MSC). The conditions at the IKET are ideal for this type of research, both in terms of equipment and technology as well as in terms of expertise in the treatment of blood and blood constituents.

Mesenchymal stem cells labelled with iron particles (electron microscopy) (Photo: Centre for Clinical Transfusion Medicine (ZKT))

Mesenchymal stem cells labelled with iron particles (electron microscopy) (Photo: Centre for Clinical Transfusion Medicine (ZKT))

Dr. Richard Schäfer heads up the mesenchymal stem cell laboratory at the IKET. The current IKET projects can be grouped into three major areas. One of these is the analysis of the differentiability of MSC. "It is absolutely necessary for the cells to be able to differentiate into fat, bone and cartilage cells. If the cells differentiate into cardiac cells, even better," said Schäfer, who is also investigating the cells’ ability to differentiate into muscle cells. This work is based on the hope of eventually being able to use the cells for therapeutic applications – for example in urology or cardiology in order to regenerate bladder sphincter or heart muscle function. Selection of the most suitable stem cells is one of the greatest challenges. MSC are a very heterogeneous family; there are hardly any specific markers available for the individual members of this family.

Dr. Richard Schäfer (Photo: private)

Dr. Richard Schäfer (Photo: private)

The second major IKET regenerative medicine project is quite different, focusing on the characterisation of MSC. Schäfer’s team is working in close cooperation with the University Hospital of Cardiac, Thoracicand Vascular Surgery. The scientists succeeded for the first time ever in developing aptamers against MSC. In a joint research project, the scientists are currently investigating the advantage of aptamers for the isolation, characterisation and differentiationi of MSC. Aptamers are three-dimensionally folded oligonucleotides that recognise specific cells. They can also be biochemically modified and immobilised on surfaces, which considerably expands their potential applications.

Where are they, where do they go and what remains?

The third major research project focuses on the destiny of MSC in organisms. In order to be able to find stem cells that have been introduced into the body, they must be labelled with detectable markers. The aim of this project jointly run with Dr. Jakub Wiskirchen’s group in the Department of Radiological Diagnostics at the UKT is to find the most suitable markers.

In the joint "Molecular Stem Cell Imaging" workgroup, scientists are analysing the labelling of mesenchymal stem cells using imaging and cell biological methods. The majority of markers used are iron particles because they can be specifically and effectively detected with imaging methods such as magnetic resonance imaging (MRI). Amongst other things, the scientists are trying to find out whether and how labelling affects the migration, settling and biology of stem cells. "We have evidence that the iron particles have an affect on the surface profile of the stem cells – at least in in vitro experiments," said Schäfer. The importance of this finding for further research and application will now be examined in further experiments.

leh - 29.11.06
© BIOPRO Baden-Württemberg GmbH, first published at www.bio-pro.de<, the Biotech/Life Sciences Portal of the State of Baden-Württemberg. All rights reserved.

Further information:

University Hospital Tübingen
Centre for Clinical Transfusion Medicine (ZKT) gGmbH
Institute of Clinical and Experimental Transfusion Medicine (IKET)

Prof. Dr. Hinnak Northoff (Medical Director)
hinnak [dot] northoff [at] med [dot] uni-tuebingen [dot] de

Dr. Richard Schäfer
richard [dot] schaefer [at] med [dot] uni-tuebingen [dot] de

Otfried-Müller-Str. 4/1
72076 Tübingen
Tel.: 07071 29-81601
Fax: 07071 29-5040