LARCEL-Andalusian Laboratory for Celular Reprograming

 

LARCEL (Andalusian Cellular Reprogramming Laboratory) is a laboratory focuses on cellular reprogramming techniques research belonging to the Ministry of Health of the Regional Andalusian Goverment in the framework of the activities of the Andalusian Initiative for Advanced Therapies. It is born in Seville in 2010 under a collaborative agreement with the Michigan State University, and the team is leaded by Prof. Jose Cibelli, Professor of Animal Biotechnology at Michigan State University (http://www.juntadeandalucia.es/csalud/larcel/en)

Since July 2014, LARCEL is located in the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND), in the Parque Tecnologico de Andalucia, in Málaga.

Our long-term goal is to provide new insights into cellular reprogramming by analyzing molecular pathways, and identifying new factors that could play an important role in cell reprogramming. The results of our work will inform the development of safe and efficient cell reprogramming protocols to be tested in pre-clinical and clinical models of human disease. Cell reprogramming is also used in our laboratory for neurodegenerative disease modeling. Whether or not a disease can be treated often depends on whether we can gain a good understanding of its basic biology. Disease modelling using iPSC technology allows scientists to explore how a disease works in the laboratory, to search affected pathways and alternative treatment.

Research lines developed in BIONAND:

Somatic cell reprogramming analysis. Identification of new factors involved in the process and analysis of pathways involved Cellular reprogramming, briefly defined as the transformation of an specialized cell into another of a different type.

When referring to cellular reprogramming in the context of induced pluripotent cells (iPSCs) we can distinguish a first step called dedifferentiation, where cells reach a pluripotent stage and subsequently induced to differentiate into specific cell types. This phenomenon was described for the first time in 2007 by two laboratories simultaneously, Prof. S. Yamanaka and Prof. J.Thomson, showing human fibroblasts transformation to pluripotent cells (iPSCs) through ectopic expression of four transcription factors (OCT4, SOX2, KLF4 and c-Myc or OCT4, SOX2, NANOG and LIN28 respectively). Although theoretically this is a “simple” protocol, cellular reprogramming is still a very inefficient process and more importantly, the molecular mechanisms governing the transformation of a somatic cell into an iPSC are still not completely understood. Cell reprogramming is also associated with cellular transdifferentiation, that is a cell from one differentiated lineage is transformed into a different differentiated cell e.g. from fibroblast to sperm without having to be go through the process of dedifferentiation first. While theoretically more simple, this approach is inefficient and is still at stages of development that are even more primitive than iPSC technologies. Nonetheless it has great appealing for future applications in cell therapy due to its safety, and therefore must be pursued in parallel with more established strategies.

Disease in a dish. Use of cell reprogramming for neurodegenerative disease modeling

Induced pluripotent stem cells (iPSCs) use is particularly useful for the study of rare diseases, specifically in neurodegenerative diseases. Nervous tissue samples from patients are rarely accessible and animal models, often do not recapitulate all characteristic of the disease. The discovery that somatic cells from patients affected by neurological disorder can be reprogrammed to a pluripotent state (iPS cells), and once reprogrammed, these cells can expand and differentiate into specific populations of neurons, opened a promising field for research and understanding the molecular and cellular basis of these abnormalities and the development of specific drugs. Our short term goal is to generate iPSCs and specific cell types affected in different neuropathies such as Ataxias, multiple sclerosis, West syndrome and Huntington disease among others, and to develop in vitro models in which perform functional assays to uncover altered cellular pathways that may explain the origin of the specific pathological states. Through scientific collaborations we anticipate the discovery of new drug targets that may enable the development of pharmacological interventions.

Zebrafish as a model to study cell reprogramming

We study the role of certain non-canonical histone during zebrafish development to bring light to reprogramming process.

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