Project Group "Regenerative Technologies for Oncology"

Fraunhofer Institute for Interfacial Engineering and Biotechnology

The project group "Regenerative Technologies for Oncology" of the Fraunhofer IGB was established in 2009. At the same time the Department of Tissue Engineering and Regenerative Medicine at the University of Würzburg was founded. The project group benefits from the synergy of leveraging the research of the Fraunhofer IGB and the Medical Faculty of the University of Würzburg.

Fields of research

In Germany, about half a million people come down with cancer each year and about a quarter of a million people die annually. Cancer (after cardiovascular diseases) is the second leading cause of death in Germany. Cancer cells grow uncontrollably and form their own nutrient-supplying blood vessels. Many tumor cells move through the blood or lymphatic system to distant organs where they build metastases which often lead to incurable cancer. Therefore, an important goal of our work is to discover the mechanisms of cancer growth, metastasis and the distribution of metastases in the human body.

  • Development of three-dimensional human tumor models as test systems

Our project group focuses on the development of three-dimensional human test systems for the development of cancer drugs. Tissue-specific vascularized in-vitro tumor models are going to be established by using of primary cells as well as tumor cell lines. Moreover, the project group is going to produce human vascularized tumors by using the Fraunhofer IGB Cell and Tissue Engineering Department’s methodology of growing human tissue with a functional blood vessel equivalent in vitro: for this purpose a bioreactor system will support the artificial tumor tissue via blood vessels as it is realized in the human body. By using this model, molecular mechanisms of angiogenesis (the formation of new blood vessels) and other relevant mechanisms of tumor formation and metastasis are going to be analyzed in future. Additionally, by using such tumor models, we’ll be able to study in which way new drugs are distributed within a tumor and how they reach their target destination. By means of these tumor models, we’re going to create new cancer diagnostics and therapeutics, avoid animal tests and are going to get validated results in vitro which will be comparable to human tumors directly.

  • Investigation of tumor stem cells and their niches

Another focus of our studies is the investigation of tumor stem cells and their microenvironment (niches) by using these in-vitro tumor models. These tumor stem cells infrequently proliferate and for this reason are quite insensitive to chemotherapeutic agents or to radiation therapies. This resistance hampers effective therapy and can even lead to relapse as well as to metastasis. Evidence suggests that tumor stem cells are sheltered from damage by their microenvironment (their niche). If we would be able to simulate such a tumor stem cell niche in vitro, we would be able to look for agents which selectively damage these tumor stem cells.

Good to know

  • How does a tumor evolves?

Strictly spoken, cancer is a side-product of evolution: mutations are generated during the replication of DNA and – on the one hand – can improve the organism’s fitness but – on the other hand – can promote cancer if the mutations affect proteins which are involved in cell cycle regulation. Most mutations don’t have any effects for the organism or are eliminated by specific repair mechanisms. However, an increasing number of mutations (e.g. induced by radiation or carcinogenic chemicals) can lead to an enhanced risk of developing one cancer cell which produces a tumor one day. Tumor cells are immortal cells and proliferate into more and more tumor cells. The surrounding tissue supports this proliferation as well as the survival of these cells because cells of this surrounding tissue are induced by the tumor cells to secrete growth factors. Among others these cells secrete angiogenic substances which induce the formation of new blood vessels to supply the growing tumor. A tissue which contains vessels is described as being vascularized.

Projects

The project group works closely with the Department of Tissue Engineering and Regenerative Medicine in Würzburg.

  • Development of a skin tumor model

Based on the human three-dimensional skin model developed by the Fraunhofer IGB (Patent no EP 1 290 145B1) we want to investigate the development and progression of malignant melanomas. Malignant melanomas are a common mortal disease of the skin. In Germany, circa 24,000 people come down with this disease annually. The aggressiveness of malignant melanomas is based on their property to generate metastases quite early. Cells of these tumors are transported via blood vessels and the lymphatic system to other organs. By using molecular-biological methods we want to analyze the mechanisms of initiation of metastasis.

  • Development of an intestine tumor model

By using of human adenocarcinoma cell lines we want to build up three-dimensional in-vitro tumor models based on the BioVaSc®. These models are going to be used for testing of new cancer therapies.

  • Investigation of stroma-tumor interactions

Tumor-associated fibroblasts play an important role in tumor progression and are a possible target for cancer therapies. They are part of the connective tissue (stroma) which subdivides the organs of the body. In a tumor, all non-tumorous cells are called stromal cells, most of them are fibroblasts. As result of an injury such as a lesion fibroblasts become temporarily activated and induce proliferation of organ tissue cells which leads to wound healing. In a tumor, the fibroblasts become permanently activated and are involved in tumor progression. For this reason, cancer is often described as “wounds that do not heal” (Dvorak 1986).

  • Development of a lung tumor model

Comparable to the generation of a colon cancer model we want to establish a human in-vitro tumor model of lung adenocarcinoma by using the BioVaSc® technology. This model is going to be used for substance testing and for the investigation of tumor-stroma interactions.

  • Neurofibroma model

In cooperation with the Charité Berlin, we use cell cultures derived from Neurofibromatosis (NF)-1-associated tumors (e.g. Neurofibroma) as well as primary cells derived from healthy skin biopsies (endothelial cells, fibroblasts) to generate a three-dimensional in-vitro tumor model based on the BioVaSc® to investigate the very complex disease neurofibromatosis. We focus on the analysis of the development of malignant peripheral nerve sheath tumors (MPNSTs) which derive from originally benign tumors. Moreover, tumor-stroma interactions are going to be analyzed in this project.

  • more details

  • Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315: 1650–9.

Services

  • Production and biochemical modification of tissue-engineered electrospun 3D scaffolds
  • Isolation of primary human stem and tumor cells
  • Establishment of co-cultures for the generation of human solid tumors in vitro and tumor test systems
  • Development of specific bioreactors for various tumor models
  • Development of human vascularized tumor tissue for the establishment of individual diagnostics and personalized therapies
  • Biological cell analysis of tumor tissue: molecular-biological, histological and immunohistochemical methods, flow cytometry (FACS), including sorting
  • Target screening for new cancer therapeutics

 

Our research services can be used for the entire value-added chain in the development of cancer therapies:

  • Investigation of the active principle and/or the side effects of new drug candidates utilizing vascularized human tumor test systems
  • Use of the tumor model in the process development of optimizing drugs or diagnostics
  • Implementation and validation of in vitro tests as alternatives to animal testing at the end of the preclinical development phase
  • Efficacy experiments of new drugs that are currently undergoing evaluation for clinical use
  • Cooperation with the medical faculty of Würzburg for the organization of the clinical phases I-III

Equipment

  • Cell culture laboratories for work on safety levels S1, S2 GenTSV
  • Cell analysis: Fluorescence microscope, FACS, microdissection system, Raman spectroscopy

Publications

  • Poster: Development and validation of a preclinical in-vitro tumor test system. Nietzer SL, Dandekar G, Walles H. Forum Life Science 2011, München.