Biology of human neural stem cells. Potential for cell and gene therapy in neurodegeneration

Research summary:

The incidence of neurodegenerative diseases is steadily increasing, particularly in well-developed countries, due to the increase in life expectancy. For some of them, like Parkinson, Huntington diseases, pharmaceutical drugs are useful at early stages of the disease, but none of them really cure the disease, since they do not halt the neuronal atrophy and death process.

In this context, research on the basic biology of human neural stem cells acquires special relevance, with the prospect that healthy stem cell derivatives, after implantation, would either delay disease progression or actually cure the disease.

Our research group is interested in understanding basic self-renewal (niche factors) and developmental events leading to maturation of stem cell derivatives, using: 1) Neural stem cells, obtained from foetal or adult human tissue, and thus instructed as neural cells; 2) Embryonic stem cells derived from the inner cell mass of the blastocist, (hES cells) from which neural stem cells can be derived; and 3) Induced pluripotent stem cells (iPSCs), reprogrammed from somatic adult cells.


Generation of human dopaminergic neurons from neural stem cells.
Top panels are microphotographs of human neurons generated in culture, stained for a general neuronal marker (ß-III-tubulin, green) and Tyrosine Hydroxylase (dopaminergic marker, red). The lower panel is a merge of the two photographs, highlighting in yellow the presence of human dopaminergic neurons.

Our main research focus is thus on basic cell growth and developmental events involved in the generation of mature cells, particularly of Dopaminergic neurons, to learn how to harness the potential that stem cells may have for therapy of these devastating diseases.

Another aspect in which we are interested on is the modification of the intrinsic properties of the neural stem cells through genetic modification, to turn them into "biological mini-pumps" (for instance for the secretion of neurotrophic factors), or to instruct them or guide their differentiation towards specific, on-demand desired phenotypes after implantation. To this end we are implementing the technology of zinc-finger nucleases, to help to conduct homologous recombination. Last, we are developing nanotools to label and track the cells in vivo, and study their cell biology in culture.


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
García LópezSilvia3054650sglopez(at)cbm.csic.esTco. de Investigación y Laboratorio
Martínez SerranoAlberto3054620amserrano(at)cbm.csic.esProfesor Titular Universidad, GA
Pérez PereiraMarta3054650pereiram(at)cbm.csic.esTitulado Actividades Técn. y Profes. GP1
Rodríguez RubioMarina3054650marina.rodriguez(at)cbm.csic.esTitulado Actividades Técn. y Profes. GP1
Stancic Brina3054650bstancic(at)cbm.csic.esTco. de Investigación y Laboratorio

Relevant publications:

  • Daviaud N, Garbayo E, Sindji L, Martínez-Serrano A, Schiller PC, Montero-Menei CN. Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease. Stem Cells Transl Med. 2015 Jun;4(6):670-84. doi: 10.5966/sctm.2014-0139. Epub 2015 Apr 29. PMID:25890124
  • Ramos-Gómez M, Seiz EG, Martínez-Serrano A. Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain. J Nanobiotechnology. 2015 Mar 5;13:20. doi: 10.1186/s12951-015-0078-4. PMID:25890124
  • González-Sánchez HM, Monsiváis-Urenda A, Salazar-Aldrete CA, Hernández-Salinas A, Noyola DE, Jiménez-Capdeville ME, Martínez-Serrano A, Castillo CG. Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state. J Neurovirol. 2015 Apr 8. [Epub ahead of print] PMID:25851778
  • Pino-Barrio MJ, García-García E, Menéndez P, Martínez-Serrano A. V-myc immortalizes human neural stem cells in the absence of pluripotency-associated traits. PLoS One. 2015 Mar 12;10(3):e0118499. doi: 10.1371/journal.pone.0118499. eCollection 2015. PMID:25764185
  • Martínez-Serrano A, Castillo CG, Courtois ET, García-García and Liste I (2011) Modulation of the generation of dopaminergic neurons from human neural stem cells by Bcl-XL. Mechanisms of action. Vitam. Horm87, 175-205.
  • García-García, E., Pino-Barrio, M.J., López-Medina, L., and Martínez-Serrano, A. (2012) Intermidiate progenitors are increased by lengthening of cell cycle through calcium signalling and p53 expression in human neural progenitors. Mol. Biol. Cell.23, 1167-1180.
  • Fernández-Cabada, T., Sánchez-López de Pablo, C., Martínez-Serrano, A., del Pozo Guerrero, F. Serrano-Olmedo, J.J., Ramos-Gomez M (2012) Cell death induction in glioblastoma cell lines by hyperthermic therapy based on gold nanorods. International Journal of Nanomedicine 7, 1511-1523.
  • Ramos-Moreno, T., Castillo, C.G. and Martínez-Serrano, A. (2012) Long-term behavioral effects of functional dopaminergic neurons generated from human neural stem cells in the rat 6-OH-DA Parkinson's disease model. Effects of the forced expression of Bcl-XL. Behav. Brain Res.232, 225-232.
  • Seiz, E.G., Ramos-Gómez, M., Courtois, E.T., Tønnesen, J., Kokaia, M., Liste I., and Martínez-Serrano, A., (2012) Human midbrain precursors activate the expected developmental genetic program and differentiate to functional A9 dopamine neurons in vitro. Short and Long term enhancement by Bcl-XL. Experimental Cell Research 318: 2446-59

Doctoral theses:

  • Javier Gonzalez Lendínez (2011). Identification and analysis of suitable human ventral mesencephalic precursors of dopaminergic neurons for cell therapy research in Parkinson's Disease. Universidad Autónoma de Madrid. Co-director: Dra. Tania Ramos Moreno.
  • Emma Green (2012). The use of zinc-finger nucleases to track the generation of dopaminergic neurons from immortalised human ventral mesencephalic neural stem cells. Universidad de Keele. Co-directores: Alberto Martínez Serrano y Tania Ramos Moreno.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand


What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: