Stem Cell Research- Regenerative Medicine
Stem Cell Research- Regenerative Medicine
By Biomedical Research Institute of Forth
The researchers of FORTH/BRI have decided to extend their research potential to stem cell research. While BRI-FORTH researchers already have a strong record in a number of disciplines, such as cell signalling, functional nuclear architecture and membrane trafficking, the extension and application of this expertise to stem cell research is expected to be highly beneficial for FORTH/BRI.
It will unlock the boundaries of current research directions and will allow a truly multidisciplinary approach of stem cell research. Expansion to a rapidly developing field with great future prospects, both in terms of basic knowledge and applications in Regenerative Medicine, is expected to generate high added value for FORTH/BRI research in the years to come.
Regenerative Medicine is an emerging interdisciplinary field of research and clinical applications, focused on the repair, replacement, or regeneration of cells, tissues, or organs to restore impaired function resulting from any cause, including congenital defects, disease, and trauma.
It uses a combi¬nation of several technological approaches that shift it beyond traditional transplantation and replacement therapies. These approaches may include, but are not limited to, the use of stem cells, soluble molecules as activators or inhibitors of physiological pathways, tissue engineering and advanced cell therapy.
Stem cells, without doubt, play a key role in Regenerative Medicine. These cells include embryonic stem cells as well as induced pluripotent stem (iPS) cells that are created from adult donor cells, such as skin fibroblasts, by eliciting the expression of a few specific genes, and thereby inducing them to become ES cell-like.
With both types of stem cells, researchers have the ability to generate and expand various types of differentiated cells for research purposes and medical applications.
By isolating cells with the potential to differentiate into multiple cell types (known as multipotent or pluripotent cells) from individuals with particular diseases, it will be possible to generate human cardiovascular cells and tissue, or any other type of cells or tissue, and therefore to study the molecular pathways that are altered between the “normal” and “diseased” state.
It will also be possible to integrate findings from these models with high-throughput genetic and chemical screening technologies and to obtain rare popu¬lations of human cells in larger quantities than presently possible.
In short, progress in stem cell technology is beginning to offer the unprecedented possibility of using human model systems to better understand the molecular causes of diseases, and ultimately to develop novel therapies.
However, before the potential of stem cells can be maximally harnessed for clinical applications, it is necessary to understand the processes that maintain pluripotency and induce differentiation.
Currently, three unique molecular properties distinguish pluripotent stem cells from somatic cells. These include a unique transcriptional hierarchy that sustains the pluripotent state during the process of self-renewal, a poised epigenetic state that maintains chromatin in a form ready for rapid cell fate decisions, and a cell cycle characterized by an extremely short gap 1 (G1) phase with the near absence of normal somatic cell checkpoint controls.
Indeed, nuclear reprogramming is currently being used to derive pluripotent cells from terminally differentiated counterparts (induced pluri¬potency), an extremely hot area of stem cell research.
A number of FORTH/BRI groups (S. Georgatos, F. Fackelmayer, T. Papamarcaki, and A. Politou) have excelled in the fields of nuclear organization and chromatin dynamics, and extension of their research into stem cells is a logical next step to make maximal use of the expertise as a firm foundation for research and applications in Regenerative Medicine.
Tissue engineering still faces many challenges, including the isolation and expansion of appropriate cell types, the arrangement of assorted cells into correct spatial organization and the creation of the optimal microenvironments for growth and differentiation.
Until now, successes have been restricted to relatively thin or avascular structures (for example, skin and cartilage), where post-implantation neo-vascularisation from the host is sufficient to meet the implant’s demand for oxygen and nutrients.
Vascularisation remains a critical obstacle in engineering thicker, metabolically demanding organs, such as the heart muscle, brain and liver. The ability to vascularise tissue constructs would be a significant step forward in tissue engineering and Regenerative Medicine.
FORTH/BRI researchers (T. Fotsis and P. Kouklis) have long-termed experience in the fields of angiogenesis, endothelial cell signalling and endothelial cell interactions.These teams closely collaborate with the groups of C.Murphy and S. Christoforidis, who are experts on membrane trafficking and endosome dynamics, processes that greatly influence cell signalling.
Together, they have a unique expertise in growth factor signalling (TGFβ/Activin A/BMP4, Wnt, VEGF), membrane trafficking thereof, and cadherin-dependent cell-cell contact mechanisms. This expertise is highly relevant to self-renewal and differentiation of human stem cells to mesendoderm-derived tissues (such as heart, liver, pancreas, blood and vessels) and generation of vascularised tissue-engineered constructs. As tissue engineering is based on biopolymer scaffolds, the team of G. Floudas, which is working on the dynamics of the self-assembly of biopolymers, will be valuable.
Two additional teams have solid background in the mechanisms of cell senescence and apoptosis (E.Kolettas) and pathways determining neuronal cell death and neurogenesis (T.Michaelidis), research domains that are important in stem cell research.
One team is exceptionally strong in mathematical modelling and meta-analysis (J. Ioannidis) and will contribute its expertise in data analysis. Finally, the team of D. Fotiadis is strongly activated in the fields of Biomedical Engineering and development of Intelligent Information systems.
It has an internationally acknowledged excellence in conducting high quality scientific research and developing innovative Information Technology (IT) applications, products and services.
Rather than trying to maintain excellence in the limited fields of each team’s research domain, joining forces and complementing their skills in stem cell research is expected to provide a tremendous added value to FORTH/BRI researchers.
Indeed, the versatile and highly qualified expertise of FORTH/BRI researchers will allow tackling of stem cell research at many levels, from cell-cell contact to signalling and nuclear programming, and from self-renewal to differentiation and engineering vascularised tissue constructs.
Moreover, stem cell biology and Regenerative Medicine is a field of rapid scientific growth and increasingly growing funding. The momentum for stem cell research in most top European centres is extremely high. If FORTH/BRI is to enhance its competitive¬ness in the coming decade, extending its capacity to stem cell research is a strategic step towards this purpose.