Summary of projects: induced pluripotent stem (iPS cells)
 – Making iPS cells from human Cord Blood or patient fibroblasts using new pluripotency factors by modified RNa transfection methods.
– Making iPS from mouse tail fibroblasts: The aim is to use the mouse model to test the pluripotent status of iPS cells made from new pluripotency factors by testing with a functional method for pluripotency, namely, making chimera and tetraploid complementation mice.
– Modeling human disease with iPS cells

Modelling human disease with iPS cells

Spinal cord injury
Spinal cord injury is a major disability resulting in huge economic loss and personal quality of life loss.  In Spain the incidence of spinal cord injury (SCI) has been estimated at the rate of 15.5 per million population (18.8 for males, 14.9 for females). In addition to physical therapy, the best strategy for treatment of spinal cord injury is to re-myelinate existing motor neurons by oligodendrocytes and to promote survival of cells against apoptosis in the injury site that undergoes a massive immune response post-injury. Recently, the development of induced pluripotent cell (IPS) technology, that uses 3 or 4 genes (Oct4, Sox2, Klf4 with or without c-Myc) to reprogram somatic cells similar to embryonic stem cells, has given rise to potential new patient specific cell replacement therapies for spinal cord injury (SCI) and other medical conditions.

Rett syndrome (collaboration project)
Rett syndrome (RTT) is a severe neurodevelopmental disorder, with a cumulative incidence of 1 per 10,000 females by the age of twelve years in Australia [JC33], and is an important cause of severe intellectual disability. Many patients display the “classic” clinical course of progressive loss of intellectual functioning, fine and gross motor skills, deceleration of head growth and the emergence of stereotypic hand movements at 6 – 18 months after birth [JC36]. However, RTT patients with a much broader clinical phenotype than originally described have been diagnosed – both milder and more severe. Although the gene responsible for most cases of RTT was identified in 1999, the pathogenic mechanisms remain largely unknown and specific targeted treatments are yet to emerge. Consequently, management remains symptomatic . It was believed that the brain dysfunction associated with RTT was permanent; however, recent studies in a RTT mouse model yielded the surprising but exciting prospect that in fact the neurodevelopmental consequences may be reversible. This has re-ignited a surge of interest in the prospect of identifying specific therapies in humans. Essential for this, however, will be a deeper understanding of the pathophysiology of RTT.

Mitochondrial respiratory chain disorder (collaboration project)
Mitochondrial respiratory chain (RC) disorders are among the most common inborn errors of metabolism with an estimated incidence of 1 in 5000 births. The majority of these disorders present during infancy with a median age of onset at 3 months and median survival rate of 12 years of age. The mitochondrial RC consists of 5 multimeric protein complexes that carry out oxidative phosphorylation to generate ATP, which supplies energy for all organs. Hence, mitochondrial RC disorders can affect any organ, but most commonly those with high energy demands such as brain, heart and muscle. Clinically mitochondrial RC defects show marked inter- and intrafamilial phenotypic variability. The nervous system is most commonly affected with ~45% of children presenting with neurologic signs.

Homozygosity mapping and high throughput sequencing strategies will lead to the discovery of novel genes responsible for mitochondrial respiratory chain disorders. iPS technology can be used to convert patient fibroblasts into clinically relevant cell types for functional analyses of the genetic defects identified.

Cardiac atrial fibrillation (AF) (collaboration project)
Atrial fibrillation (AF) is the most common heart rhythm abnormality in our community and is a major risk factor for stroke and heart failure. Recent data suggests that genetic factors contribute significantly to the pathogenesis of AF but very little is known about what these genes might be and how gene variations can cause disease. It has been recently discovered that over-expression of four genes (known as the “four factors”), OCT4, Sox2, Klf4 and Myc can re-program cells into iPS cells. The recognition that iPS cells can be used to make any cell of the human body is one of the most significant scientific advances in the past decade and offers new possibilities for studies of the causes and treatment of human disease.

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Facultat de Medicina
Departament de Ciències Fisiològiques I
Casanova, 143
08036 Barcelona
Tel. & Fax: 93 403 52 78

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El Ministerio de Economía y Competitividad


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