Stem Cell-Based Translation
The CEO of ISSCR, Nancy Witty, is still convinced that Hamburg is a beautiful city that would make a great destination for ISSCR’s Annual Meeting. “The tremendous support and strong scientific German stem cell community, Life Science Nord, and the City of Hamburg were all significant considerations in our selection of Hamburg as our host city. While we are disappointed that we will not be able to gather in person in June, we are pleased that we will be in Hamburg for our 2024 annual meeting,” Witty says.
“We are pleased that the ISSCR Annual Meeting will be in Hamburg 2024.”
“We were enthusiastic about the ISSCR decision for Hamburg”, says Ole Pless, Head of Translational Drug Discovery at Fraunhofer ITMP ScreeningPort, who coordinated the pitch for the congress as scientific adviser and is well connected in the scientific stem cell community. Apart from being an ideal location for top tier scientific conferences, Hamburg and Schleswig-Holstein can indeed build on a very dynamic research and development landscape in the field of stem cells. This article highlights just some of the current translational stem cell-based approaches that are being developed in the North.
As a constant source of new living cells, stem cells come in two types: Adult stem cells represent the body’s natural reserve for the regeneration of tissues and organs. These stem cells reside in the tissues of the body and produce a constant supply of new cells to replace cells that are worn out or damaged.
The other type of cells are pluripotent stem cells. These cells can develop into almost any of the more than 200 variants in the human body. Pluripotent stem cells include both embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells). The latter can be obtained by reprogramming - a technology that has revolutionized the field in the past decade. Reprogramming converts adult human cells into iPS cells using a range of transcription factors. iPS cells are an infinite source for the generation of any cell type.
"Stem cells help us to build better and more realistic disease models for pharmaceutical research and preclinical development."
The Fraunhofer Institute for Translational Medicine and Pharmacology ITMP ScreeningPort is a translational medicine research center, based in Hamburg, which specializes in searching through its huge collections of small molecules for hits with the potential to be developed into drugs.
"Stem cells help us to build better and more realistic disease models for pharmaceutical research and preclinical development," explains Pless. One example of a neurodegenerative disease studied by the Fraunhofer researchers is multiple sclerosis (MS). MS is the most common chronic inflammatory disease of the central nervous system. A novel strategy that MS researchers are pursuing worldwide in academics and the pharmaceutical industry is to make nerve cells in the brain more resilient to stressors: They are keen to find drugs with neuroprotective properties.
The Fraunhofer researchers collaborate closely with Prof. Manuel Friese, the director of the Institute of Neuroimmunology and Multiple Sclerosis (INIMS), a translational research institute at the University Medical Center Hamburg-Eppendorf (UKE). One potential drug target identified by Friese’s team is TRPM4, an ion channel in nerve cells. Chronic inflammation causes the ion channel to be hyperactive and a permanent sodium influx eventually harms and kills the neurons. Together with the Fraunhofer IME/ITMP ScreeningPort and biotech company Evotec SE, Friese’s team aims at developing a neuroprotective drug that can be taken orally. The consortium has already identified small molecules that function as effective TRPM4 inhibitors.
"We have created a versatile toolbox based on iPS cell technology to test the inhibitors directly where they should act therapeutically: On human neurons,” says Pless. The promising research again gained the support of the German Federal Ministry of Education and Research (BMBF) for the third successive project and received 1.2 million euros as part of a program for the validation of disease-related target structures. The aim of the project is now to learn more about TRPM4 as a possible target structure and the drug candidates in order to reduce the nerve damage specifically responsible for the progressive worsening in MS patients.
Modelling organ systems
Another trend aims at engineering miniature organs or specialized tissues in the lab and combining them to create multi-organ systems: In the interdisciplinary research project “HiPSTAR”, Fraunhofer researchers use patient-derived cells to decipher the molecular mechanisms leading to Alzheimer’s disease. They have constructed an iPS cell-based model of the human blood-brain barrier (BBB) which serves as a protective but selective barricade between the sensitive brain and the blood circulation. The in-vitro model can serve as a research tool to develop drugs with brain-penetrating properties or to identify novel disease-specific targets. The BBB models are currently being validated with approved and marketed drugs and compared to conventional models. The BMBF has contributed 1.7 million euros in funding for the project.
Thomas Eschenhagen and his team at the UKE and the German Center for Cardiovascular Research (DZHK) are a powerhouse of translational stem cell research in the North. They specialize in engineered heart tissues (EHTs), three-dimensional muscle constructs that can be generated from iPS cells and other stem cells. The Hamburg-based spin-off EHT Technologies GmbH with CEO Arne Hansen constructs test systems that are powerful tools for pharmacological research and drug development. The team headed by Christine Klein from the University Hospital Lübeck is specialized in the stem cell-based research of Parkinson’s. As partner of the European StemBANCC consortium, the researchers coordinated the formation of a bank of patient-specific iPS cell lines as a resource to study mechanisms of Parkinson’s and other movement disorders, paving the way for the development of new drug targets.
Diverse range of approaches
“iPS cells have opened doors where other technologies failed,” says Lanthaler, the CEO of Evotec SE. Not only in the field of neurodegenerative disease, iPS technology provides an excellent tool for disease modelling and predicting drug efficacy.
“In terms of the scope of the platform and the systematic integration of the iPSC platform to all other drug discovery technologies, we are at the forefront of the whole industry.”
Over the last decade, Evotec has built an iPSC-based platform to meet the highest industrial standards in terms of throughput, reproducibility and robustness. Evotec’s iPSC team has grown to more than 150 people. It plays an essential role in longtime alliances with strategic partners, such as Bristol Myers Squibb (formerly Celgene). “In terms of the scope of the platform and the systematic integration of the iPSC platform to all other drug discovery technologies, we are at the forefront of the whole industry,” Lanthaler says. In recent years, Evotec has developed its platform to use iPSC-based cells in cell therapy approaches, e.g., in diabetes.
And in December 2020, Evotec and Sartorius have entered into a partnership with Curexsys GmbH, a Goettingen-based specialist in the emerging field of therapeutic exosomes. These are small vesicles which are derived from human Mesenchymal Stem Cells (MSCs). Increasing evidence suggests that exosomes can aid tissue repair and engineering vesicles could carry drugs to diseased tissue. Thus, they may represent the next generation of therapeutics in regenerative medicine.
Cell culture technology and cell logistics
Several players in the North are also providers of much-needed stem cell technologies: Eppendorf AG provides bioreactors and bioprocess technology for stem cell cultivation. PerkinElmer Cellluar Technologies produces high-content imaging systems that are used in stem cell-based screens. PeproTech GmbH is a lab provider specialized in cell culture media.
The Kiel-based start-up Cellbox Solutions GmbH constructs portable incubators for the transportation of living cells. These high-tech boxes provide a safe environment for the transport of living cells and biological structures under laboratory conditions, e.g., at 37°C and 5% CO2. The idea was born at the Fraunhofer Research Institution for Marine Biotechnology and Cell Technology (EMB) in Lübeck. Founded in 2017 by Prof. Kathrin Adlkofer and currently managed by CEO Wolfgang Kintzel, today Cellbox affords 15 employees and is anticipated to grow further. Apart from stem cell research and the growing cell therapy market, the start-up also caters to the in-vitro fertilization market.
Author: Philipp Graf
Biotech & Pharma