ABOUT STEM CELLS
Research on adult stem cells, in particular haemopoietic cells in the bone marrow, is a long tradition in Switzerland. On the other hand, since their first derivation in 1998, human embryonic stem (ES) cells derived from donated in vitro-fertilized spare embryos have focused a lot of attention, hope and ethical debate.
In Switzerland, the legislation presently allows research on human ES cells. Indeed, the 2003 Stem Cell Research Act, which was approved by popular vote in November 2004 and came into force in 2005, allows Swiss researchers to either derive or import human ES cell lines.
Several groups are conducting research projects on ethically approved scientific questions not pursuable through other means under licences granted by the Federal Office of Public Health.Stem cells are found in most, if not all, multi-cellular organisms. They are characterised by the ability to renew themselves through mitotic cell division and differentiate into a diverse range of specialised cell types.
Thus, any source of stem cells, whether from embryonic, fetal or adult tissues is of great interest for regenerative medicine aiming at regenerating damaged tissue with new functional cells. Tissue regeneration options include the injection of stem cells or progenitor cells, the transplantation of tissues grown in vitro, or the induction of regeneration by molecules, growth factors or introduced substances, thus busting the auto-reparative capacity of a damaged tissue to better recruit its endogenous pool of stem cells.
The Swiss stem cell networks created in 2004 offers a comprehensive list of the Swiss research groups working on stem cells. Several teams in the BioAlps cluster are conducting both fundamental and clinically-oriented research projects based on stem cells.
There are three teams at the University of Geneva working with human ES cells: one at the Geneva University Hospitals (Dept of Gynecology and Obstetrics) studying pluripotency in both ES and induced pluripotent stem cells (iPSC), and two at the Faculty of Medicine (Dept of Pathology and Immunology). One of these teams investigates the molecular mechanisms cardiogenesis in both mouse and human ES cells and develops cellbased strategies for the regeneration of the infarcted myocardium using animal models of myocardial infarction.
Specifically, tissue engineering strategies include the use of cell-seeded biodegradable matrices or cardiopatches for tissue repair. It has recently begun a national collaboration with two groups at the CHUV and the Zurich University Hospital to implement an optimized cell therapy option for the heart in large animal models of myocardial infarction.
The second unit works on neurodegeneration and is particularly interested in the neuronal differentiation of embryonic stem cells, focusing on basic mechanisms of neuronal differentiation and the production of dopaminergic neurons for the treatment of Parkinson’s disease. This latter topic is part of a multidisciplinary consortium called “Prometheus”, led in collaboration with the Faculty of Medicine and the Geneva University Hospitals.
Among several adult stem cell groups, Geneva University’s Department of Genetic Medicine and Development is researching stem cells and precursors in the brain, with the possibility that the Sonic hedgehog-Gli pathway might be used to stimulate proliferation / replenishment of cells that give rise to neurons derived from responsive precursors. The research team studies the role and the potential of Gli proteins to specify dopaminergic cell fate and to expand appropriate stem cell populations.
At the Swiss Institute for Experimental Cancer Research (ISREC),part of the EPFL School of Life Sciences, mouse genetics studies enable the investigation of tissue-specific stem cells and their role in tissue homeostasis and carcinogenesis.
Proliferation and differentiation of cells within multicellular organisms need to be precisely controlled in order to establish and maintain optimal size and function of organs. Highly regenerative tissues such as skin, gut or bone marrow rely on a strict cellular hierarchy of few pluripotent stem cells and their increasingly committed progeny. A specialized local microenvironment fosters stem cells in a niche which establishes a complex interaction network controlling stem cell function.
Since multipotent, self-renewing stem cells persist within a tissue for long periods of time,they have a much higher probability to accumulate mutations than most mature cell types. This suggests that many sporadic tumours may arise from tissue-specific stem cells. Therefore, understanding the signalling networks that control stem cell proliferation. and commitment in normal tissue homeostasis will also provide insights into mechanisms that underlie tumour genesis.
… TO TRANSLATIONAL RESEARCH
The Gene therapy and Stem cell biology unit of the Lausanne University Jules-Gonin Ophthalmic Hospital is carrying out original research using viral vectors for experimental therapy to treat different forms of retinal degeneration as well as to exploit therapeutic effects of antiangiogenic gene transfer. Specifically, they are investigating gene transfer into the cornea, the isolation and culture of human retinal stem cells; the identification of factors that trigger proliferation and survival of stem cells in mouse retina; as well as stem cell transfer into human and mouse retina.
The EPFL School of Life Sciences includes a Laboratory of the dynamics of stem cells (LDCS) which is working on both understanding the fundamental biological processes of stem cells and their clinical application. LDCS is developing in vitro and in vivo models (cell cultures and animal models) to improve stem cell treatment in humans for severe burns, pointing at the reconstruction of hair follicles and sweat glands, as well as investigating gene therapy for epidermolysis bullosa, a severe dermatological condition. Hematopoeitic stem cell transplantation is currently carried out in specialised hospitals in Switzerland.
In the BioAlps cluster, the Geneva University Hospitals are the specialised centre. There have been a certain number of gene therapy clinical trials in Switzerland, notably in the area of cancer, HIV and ALS. The majority of vectors are based on viral vectors and the majority of trials focus on cancer immunization. Gene therapy clinical trials are regulated in Switzerland by Swissmedic for in vivo trials, Swiss Federal Office of Public Health for ex vivo trials.
Beyond research, several companies have actually begun to supply researchers with stem cells and derivatives. Stemedica is a specialty biopharmaceutical company that is committed to the development and manufacture of best-in-class adult stem cells for use by approved research institutions and hospitals for preclinical and clinical studies. It has a cell manufacturing and master banking unit in Switzerland.
Biosafe, an internationally active medical technology company, is offering industry standards in adult stem cell therapy, developing, manufacturing and supplying innovative solutions for cell processing in both stem cell banking and regenerative medicine. If you are working in this field in Western Switzerland, please join our network and let us know what you are doing. It will give you more exposure and wider reach and increase our knowledge base. You can get in touch with us at: .