Cluster of Excellence

From

Regenerative Biology to Reconstructive Therapy

Hannover Medical School

& Partners

Establishing an excellent cluster

The goal of the Excellence Initiative is to strengthen cutting-edge research in Germany and to improve its international competitiveness. Outstanding projects are funded as Clusters of Excellence which focus the research potential at university locations in Germany and, hence, strengthen their international visibility. With the enthusiastic support of six important partner institutions, Hannover Medical School (MHH) has established a Cluster of Excellence in the area of Regenerative Biology and Reconstruc tive Therapies, acronym REBIRTH. REBIRTH receives funding over a period of five years with an average budget of 6.5 million euros per year.

REBIRTH Optimal partner

The Hans Borst Center for Heart and Stem Cell Research was funded with 13.5 million euros by the Braukmann-Wittenberg Heart Foundation. Since May 2008 13 of 40 working groups are based in the new building.

Our programme integrates excellent training with innovative science and experimental as well as clinical medicine. Interactive basic research projects are designed to identify and evaluate cellular and molecular mediators that stimulate regeneration.

We test new approaches for regenerative therapies using novel (if possible somatic) cell sources which we engineer applying genetic, epigenetic, as well as scaffold-based principles. Expertise in various fields of engineering, chemistry, biophotonics and nanotechnology supports and supplements our research and development. Toward patient-focused, applied studies, the existing wide range of certified/accredited facilities for Good Practice (laboratory,

manufacturing and clinical) and close industrial collaborations will be further expanded. Upscaling technologies and pro-active biosafety assessment complete our translational activities. Based upon MHHs recent key achievements and priorities we focus on disorders of blood (including immunity), heart, lung (respiratory tract), liver, and pancreatic beta cells.

Approval

Established Therapy

Feedback

Area C
GLP, GMP, GCP Upscaling MolTox/ Pathology Imaging

Good practice and Pharmacovigilance Clinical trials

Reconstructive Therapy
Tissue Engineering/ Functionalized Implants Cell Therapy Regenerative Agents

Area B

Disease models

Blood

Heart

Lung

Liver

Regenerative Biology
Phylogeny Ontogeny Milieu Cell Proliferation (Epi) Genetics

Area A

Stemness

Reprogramming
Differentiation

Function

Area D
Education Ethics Public Relations

Gender Equity

Human Resources

Cultural Diversity

REBIRTH - Cluster of Excellence in the area of Regenerative Biology and Reconstructive Therapies. We focus on disorders of blood (including immunity), heart, lung (respiratory tract) and liver in a disease specific way.

Thereby, REBIRTH represents an optimal partner for other domestic and international centres in regenerative medicine.

Hannover Medical School

Max Planck Institute for Molecular Biomedicine, Mnster

Area A: Regenerative Biology and Related Sciences

Our basic research activities in Area A are conducted by two collaborative research units that focus on Stem Cell Biology and Regeneration and Organogenesis. Key objectives of our work programme are to obtain deeper insights into the basic mechanisms of genetic and epigenetic reprogramming, allowing us to develop novel pluripotent cell sources potentially derived from postnatal tissues, and to control their differentiation with subsequent robust functional tests.

Discovering novel therapeutic targets

The field of stem cell biology will receive a new twist by addressing the biochemical and genetic basis that forms the sweet surface of stem cells, with potentially immense implications for their homing, migration, differentiation and labeling. Furthermore, we wish to identify key players of organogenesis and compare these to the regulators of milieu-dependent regeneration. Finally, we explore intrinsic and extrinsic limitations of regeneration by studying mechanisms of cell cycle control, senescence and ageing. This work is designed to discover novel therapeutic targets Rational drug design produces and methods. Area A has multiple inisoform-specific inhibitors that target a novel allosteric teractions with Area B.
binding site in myosin.

 Christian Richters, Mnster

Helmholtz Centre for Infection Research, Braunschweig

Federal Research Centre for Animal Health, Mariensee

Area B: Reconstructive Therapy in Preclinical Models

Area B connects insights from Area A with input from clinical practice and translational platforms (Area C). To replace dysfunctional organs and tissues or to restore their function, we focus on cell therapy and tissue engineering.

The search for novel regenerative agents and biomaterials is embedded in these activities. In preclinical models of human diseases affecting lymphohaematopoietic system, heart, lung, liver and pancreatic beta cells, we address the therapeutic options provided by different cell sources (adult vs. embryonic) and the combination of cell therapy with regenerative agents.

Therapeutic initiatives conducted in networks

This research is flanked by programmes investigating modes of inducing tolerance to cells that are not entirely self. Most of our therapeutic initiatives are coupled to ongoing clinical trials, some of which are conducted in national and international networks. Especially for cardiovascular and pulmonary indications, we will study the potential of clinically applicable 3-dimensional bioartificial tissue composed of cell-seeded biological or synthetic matrices. This includes the functionalization of synthetic (and biodegradable) implants by nanostructuring, coating with bioactive compounds and pre-implantation cell seeding. Novel technologies based on biomechanics and photonics connect regenerative medicine with physical, mechanical and chemical sciences.

University of Veterinary Medicine Hannover

Leibniz University of Hannover

Area C: Translation

Area C will supply important tech nological platforms for Areas A and B and will be essential for translation of developments from Area B into clinical application. To follow the effects of recombinant agents and modified cells or tissues in vivo, we will further strengthen our investments in bioimaging and cell marking (genetic and phenotypic), and study the long-term integrity of engineered and clonally expanded cell populations in the homeostatic, stressed and ageing organism (interaction with Areas A & B).

Including integrated concept for GXP

Included in this global assessment are the derivation, expansion, manipulation, and characterization of human stem cell lines, as well as preclinical efficacy and toxicity testing in appropriate animal models. Large-scale cell expansion and biocompatibility testing are further important translational topics. Potential toxicity will be primarily addressed by investigating genetic and epigenetic instability and inappropriate differentiation. Our translational activities include an integrated concept for GXP: good practice for laboratory, manufacturing and clinical work (GL P GM P GCP). Clinical projects are supervised to guarantee highest quality already in preclinical data collection, product design, For mammalian cell cultivation probiocompatibility testing cesses, main research topics are the influence of environmental paraand finally the conception, conduct meters such as shear stress, temperature and toxic metabolites on cell and data management of clinical behaviour and productivity. trials.

Laser Zentrum, Hannover

Fraunhofer ITEM, Hannover

Area D: Human Resources

REBIRTH considers the promotion and integration of young scientists and the gender equality programme as key indicators of its performance. The emphasis on education and equality is an integral component of our scientific programmes, and we believe that an own Area dedicated to these important topics is as relevant for the long-term success of REBIRTH as the quality of our research activities.

Establishing an interdisciplinary PhD programme

The first step in this direction was the establishment of an interdisciplinary international PhD programme Regenerative Sciences. It covers all crucial topics ranging from basic biology of regeneration over principles of engineering technologies (materials, cells, tissues) to clinical study design and related questions (good practice, process development, regulatory, economical and ethical issues). As part of all activities, REBIRTH will also strengthen the investment of its participating institutions to promote gender equality.

Supporting career development

One component of this task is to implement effective career development measures. These shall be further expanded to include long-term career perspectives of international colleagues in Germany. An integrated approach to increase diversity and obtain long-term feedback of alumni is thus a logical consequence of our work.

Cluster of Excellence From Regenerative Biology to Reconstructive Therapy

Longterm objectives
n

We envision that REBIRTH will reach the following goals:

to form a centre for basic and translational studies on stem cells and tissue engineering in hematopoietic, cardio-vascular, respiratory and hepatopancreatic medicine, leading to innovative therapeutic strategies to create an internationally renowned major player in the design and implementation of regenerative clinical studies with a strong emphasis on biosafety and predictability to realise trans- and intrainstitutional networking by forming dual leaderships of clinical departments and technical/naturalscientific institutes with a regenerative focus to strengthen our position as an attractive national and international networker, characterized by an interdisciplinary culture of open-minded, hypothesis-driven and innovative research.

REBIRTH - Cluster of Excellence Hannover Medical School Carl-Neuberg-Str. 1 30625 Hannover, Niedersachsen, Germany Coordinator: Professor Dr. Axel Haverich Business Manager: Tilman Fabian Tel: +49 511 532 - 5204 Fax: +49 511 532 - 5205 info@rebirth-hannover.de www.rebirth-hannover.de www.mh-hannover.de

March 2009