Our group is focused on morphological and dynamic studies of the organisation of adult neurogenic zones of the central nervous system, and their comparison from fish to mammals (including the human species). We have pioneered the identification of areas of adult neurogenesis, as has been the case in reptiles and other vertebrates, and the identification of the stem cells responsible for such neurogenesis, as has been the case in fish, birds and mammals. These comparative studies have been very useful, allowing us to discover the existence of a cilium that acts as an antenna and is essential for activating neurogenesis. This discovery has helped cancer research groups to use it as a therapeutic target.
One of our main lines of research is based on the study of the activation or modulation of these areas in neurodegenerative diseases, as well as the potential effect on the activation of neural stem cells (NSCs), neurogenesis and oligodendrogenesis for myelination. On the other hand, we are not only dealing with problems with endogenous cells, but we have also tried to use exogenous stem cells, from bone marrow and fat. To this end, we have developed a number of techniques, notably the refinement of immunolabelling for electron microscopy in order to be able to monitor transplanted cells.
Among the models with potential clinical use, we have chosen cerebral stroke and multiple sclerosis (MS). In the case of stroke, we have transplanted human mesenchymal stem cells (hMSCs) and multipotent adult progenitors (hMAPCs), observing that cell transplantation provides neuroprotection and prevents secondary brain damage. This neuroprotective function is mediated through different therapeutic effects such as induction of angiogenesis, decreased inflammation and scarring, and increased proliferation of NSCs. In the case of the MS, we used classical MOG peptide lesion models and injected factors for oligodendrocyte activation, invading adjacent areas. Within the transplantation line, and in collaboration with the University of San Francisco, we have performed transplants of the medial ganglionic eminence from mouse embryos into early postnatal mice. Because the transplanted cells were fluorescent (GFP) we were able to analyse their distribution in the cerebral cortex and surprisingly and contrary to what is accepted, at least for the central nervous system, neuronal populations determine their number intrinsically, rather than due to external factors.
Other ongoing research is the discovery of the existence of neuronal migrations that take place in the human brain from the ventricles to the prefrontal cortex. These migrations are rarely observed in a very short window of life, ranging from embryonic stages to 6 months of life. We interpret this as our brain's ability to rapidly increase the cell population of the prefrontal cortex, which is well known for its importance in memory and learning.
Finally, we have observed that some of these chains appear to be directed to other regions as well, which would add valuable novel information unique to mammals. This series of findings are part of a macro-project, which aims to learn more about the fine and functional organisation of the human brain, and which is framed by other discoveries of ours such as the existence of stem cells in our brain, which helped to change the idea that there are no new neurons formed after birth.
Last but not least, we are a national and international reference in electron microscopy techniques for morphological diagnosis and not only for nerve cells, but also for stem cells, as confirmed by our numerous collaborations.
- Adult neurogenesis in humans.
- Use of stem cells in stroke and multiple sclerosis models.
- Oligodendrocytes and myelin.
- Marking techniques.
- Cell therapy in an animal model of multiple sclerosis. Genetic modification aimed at enhancing axonal regeneration
The project deals with the application of cell therapy with genetically modified mesenchymal cells (episomal plasmid) to treat progression and repair neurological deterioration in the animal model of multiple sclerosis.
- Study of oligodendrocytes and their capacity for myelination during development and in the full grown adult
The aim is to analyse the myelination process during development, which are of vital importance for the induction of myelination/remyelination processes in the adulthood. In demyelination models, remyelination will be analysed using the acquired knowledge.
- Morphological and molecular characterisation of exosomes. Study of their metastatic potential in cancer
Exosomes have been discussed in science as a possible route for long-distance communication, using vesicles. They contain proteins and nucleic acids. The project aims to learn more about these vesicles in blood, their morphology and molecular content from metastatic cancer.
- Ageing and Alzheimer. GSK3 as a therapeutic target
The project aims to analyse NSCs, neurogenic niches and neurogenesis with age, as well as their involvement in AD. On the other hand, the role of GSK3 in the proliferation and differentiation processes of NSCs both in vitro and in vivo will be studied, as well as its regulation as a target.
- Nanoparticle and biomaterial-based therapies with clinical application in cerebral ischaemia and cancer
Development of nanoparticles with functionalisation capacity for their application in bioimaging, anti-tumour therapy and regenerative therapy (Project developed by Vicente Herranz Pérez, post-doctoral researcher contracted by CIBERNED).
- Cell therapy with adult stem cells in cerebral ischaemia
The neuroprotective role of bone marrow stem cells in a model of cerebral ischaemia will be analysed. To this end, the cells will be stained with iron and directed to the location of the injury by means of magnetic fields in order to increase the number of viable cells in the injured tissue.
- Identification and characterisation of neurogenic niches in the adult mammalian brain
The overall project will identify and characterise neurogenic niches in different areas of the nervous system: the SVZ, the DG of the hippocampus, the third ventricle and the spinal cord. These niches will be analysed in different animal species from mouse, monkey to human.
- Study of the aetiology of amyotrophic lateral sclerosis and development of therapies based on the neuroprotective role of mesenchymal stem cells
We will analyse the earliest effects that occur in the neurons of the spinal cord, as well as the role played by glia, with the aim of identifying the mechanisms that cause and are involved in the disease. On the other hand, a potential pathway of propagation between neurons will be studied.
- GARCIA VERDUGO, JOSE MANUEL
- PDI-Catedratic/a d'Universitat
- DURAN MORENO, MARIA
- Alumn.-Servei de Formacio Permanent
- ExpandirGARCIA VERDUGO, JOSE MANUELPDI-Catedratic/a d'Universitat
Burjassot/Paterna Campus
Science ParkC/ Catedrático José Beltrán, 2
46980 Paterna (Valencia)
- GARCIA VERDUGO, JOSE MANUEL
- PDI-Catedratic/a d'Universitat
