Pluripotency for organ regeneration

The generation of induced pluripotent stem cells (iPSCs), especially the generation of patient-derived pluripotent stem cells suitable for disease modelling in vitro, opens the door for the potential translation of stem-cell related studies into the clinic. 

Successful replacement, or augmentation, of the function of damaged cells by patient derived differentiated stem cells would provide a novel cell-based therapy for diseases. Since iPSCs resemble human embryonic stem cells (hESCs) in their ability to generate cells of three germ layers, patient-specific iPSCs offer definitive solutions for the ethical and histo-incompatibility issues related to hESCs. Indeed human iPSC (hiPSC)-based autologous transplantation is heralded as the future of regenerative medicine.

One of our aims is to generate and correct disease-specific hiPSCs for disease modelling and drug screening. The combination of gene-editing based methodologies together with the development of novel protocols for cell differentiation into relevant tissues/organs, provides a unique scenario for modelling disease progression, and the identification of molecular and cellular mechanisms leading to organ regeneration (Figure 1). In this regard we are particularly interested in generation of transgene-free and disease free patient derived hiPSCs for disease modelling and the discovery of novel therapeutic targets.  

We believe that the recovery of tissue function should not be restricted to the development of cell replacement therapies. In this regard, in our laboratory we take advantage of organisms that possess the ability to regenerate such as zebrafish, in order to understand which molecular and cellular pathways lead to organ regeneration.

Surprisingly, studies in neonatal mice have demonstrated that soon after birth this organism posses the capability to regenerate its heart. Taking advantage of such preliminary observations we are translating such analysis in order to understand if the mammalian neonatal kidney still posses the capability to regenerate, and more importantly, if we are able to dissect the epigenetic and cellular mechanisms leading to those responses. 

Lastly, and in an effort to fully develop in vitro and ex vivo platforms for organ regeneration, in our lab we are focused in the development of reporter cell lines for different transcription factors essential for tissue-specific commitment and differentiation (i.e: renal and cardiac lineages). The possibility to combine pluripotent stem cell lines together with decellularized matrices, functionalized biomaterials and ex vivo organoids offers and unprecedented opportunity for the immediate generation of patient-specific in vitro and ex vivo platforms for disease modelling and organ regeneration (Figure 2). 

• Real Time QuantStudio 5
• SimpliAmp thermocycler
• Eppendorf 5415D centrifuge
• Allegra X-15 R centrifuge
• Gyrozen 1248 centrifuge
• BioUltra 6 Telstar culture Hood 2x
• AH-100 Telstar primary culture Hood
• Binder CB 60 incubators 2x
• Controltecnica ASTEC SCA 165 incubator
• Controltecnica ZC 180 incubator
• Bioruptor Pico sonicator
• Thermomixer C thermal block
• Leica DMS1000 and DMIL Led microscopes
• Leica DMi1 microscope
• Leica MZ 10F magnifying glass
• Safe Imager 2.0 transilluminator

• Juan Carlos Izpisua Belmonte
  Salk Institute for Biological Studies
• Dr. Josep Maria Campistol Plana
  Experimental Laboratory of Nephrology and Transplantation, Hospital Clínic, Barcelona
• Peter Hohestein
  The Roslin Institute, University of Edinburgh
• Dr. Pere Gascón Vilaplana
  Head of Oncology Service/Molecular and Translational Oncology Laboratory, IDIBAPS
• Gloria Calderon
  Embryotools SL
• Pura Muñoz Cánovas
  Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
• Dr. Pedro Guillén
  Director Clínica Cemtro, Madrid
• Dr. Francisco Fernández Avilés
  Head of Cardiology Service, Hospital General Universitario Gregorio Marañón, Madrid
• Dr María Eugenia Fernández
  Unit of Cell Production, Hospital Gregorio Marañón, Madrid
• Joaquin Gutiérrez Fruitós
  University of Barcelona
• Dr. Pere Roca-Cusachs
  IBEC
• Dr. Elena Martínez
  IBEC
• Dr. Cristina Eguizabal  Argaiz
  Centro Vasco de Transfusion y Tejidos Humanos (CVTTH), Bizkaia
• Dr. Antonio Alcaraz
  Head of Urology, Hospital Clínic, Barcelona
• Dr. Oriol Casanovas
  Head of Tumour Angiogenesis Group, IDIBELL