RESEARCH PROGRAM

Regenerative Medicine

"Cell therapy constitutes one of the essential pillars of the medicine of the future, thanks to the discovery of induced reprogrammed cells (iPS) and the consolidation of cell reprogramming."

DR. FELIPE PRÓSPER
DIRECTOR. REGENERATIVE MEDICINE RESEARCH PROGRAM

Many tissues have the capacity to regenerate thanks to the presence of stem and/or progenitor cells. In the Regenerative Medicine Program at Cima we study the mechanisms involved in stem cell biology (self-renewal, differentiation, reprogramming and maintenance of pluripotency) as well as their therapeutic application in cardiovascular diseases, osteoarticular diseases, rare metabolic diseases (such as primary hyperoxaluria) or rare muscle diseases (such as Duchenne muscular dystrophy), as well as the application of new products of advanced therapies.

The program consists of clinicians and researchers working especially with cells derived from bone marrow and adipose tissue, induced pluripotency stem cells (iPSCs), cardiac cells obtained by direct reprogramming strategies and by directed differentiation of iPSCs, myogenic precursors, and endothelial cells.

We focus on the collection and characterization of these cells, their functional study and therapeutic use. The use of cell therapies requires a specific regulation, which demands that certain requirements for their manipulation and therapeutic use are met.

 

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Objectives of the Research Program in Regenerative Medicine

To deepen the potential of stem cells
of stem cells

Identify and characterize stem cell populations as well as the mechanisms involved in tissue repair and regeneration processes.

To design new
therapeutic strategies

Validate the application of cell therapy and tissue engineering therapeutic strategies based on endogenous repair mechanisms in experimental models.

Clinical trials of
advanced therapies

Establish proof-of-concept studies through clinical trials of advanced therapies.

GMP LABORATORY

Development of advanced therapies

Cima works with the Clínica in the development of advanced therapy products under strict quality controls. For the development of these products on a clinical scale, the Clinic has a GMP laboratory, the first accredited laboratory in a hospital within the National Health System.

The GMP laboratory produces advanced cell and tissue therapy drugs under Good Manufacturing Practices (GMP) standards and is authorized by the Spanish Agency of Medicines and Health Products.

Lines of research

PI: Manuel Mazo

We are focused on generating mature human cardiac tissue in the laboratory using tissue engineering strategies, both for therapeutic application and for in vitro modeling of drug effects.

To this end, we aim to gain a better understanding of the factors that determine cardiac maturity, in addition to applying state-of-the-art additive manufacturing strategies. This will be achieved by implementing a highly interdisciplinary strategy, including advanced genomic and gene editing technology in tissue engineering models, fabrication using 3D printing strategies, intelligent materials ("smart materials") and bioreactors among others, together with cardiac phenotypes derived from human iPSCs.

Objectives:

  • To build models of diseased and healthy cardiac tissues for use in drug testing as well as precision medicine applications from the use of new fabrication strategies and biomaterials, human iPSC-derived cells and biostimulation (bioreactors).
  • Implement advanced genomics tools in the study of cardiac maturation regulation and apply this knowledge to tissue engineering.
  • Coordinate the efforts of engineers, chemists, biotechnologists and clinicians to develop a new generation of therapeutic and diagnostic tools.

PI: Xabier Aranguren

We develop new therapeutic alternatives based on the generation of xeno-organs in vivo using stem cells. This will be achieved by microinjecting pluripotent stem cells into genetically modified embryos incapable of generating a certain type of organ/cell type.

The generation of such organs could confer an immune advantage for xenotransplantation into the species of origin of those stem cells.

Objectives:

  • To generate "naïve" pluripotent stem cells from different species.
  • To produce pre-implanted organ-deficient embryos by Crispr/cas9 technique or by transgenesis.
  • To generate rat organs in murine host and primate organs in pigs.

PI: Xonia Carvajal

We are investigating to improve knowledge of the molecular pathways that control cellular self-renewal, differentiation and induction of cardiovascular progenitors, as well as to enhance the engraftment of these cells in animal models of myocardial infarction.

This knowledge will be essential for the development of protocols for future clinical application. 

In addition, we propose to establish a new direct reprogramming strategy to induce cardiovascular progenitors from somatic cells.

On the other hand, we aim to know the possible functional effect of cardiovascular progenitors in the treatment of myocardial infarction.

Objectives:

  • Identification of new biological regulators of human cardiovascular progenitors.
  • Establishment of a new methodology for direct reprogramming of human fibroblasts into cardiovascular progenitors.
  • Use of new approaches to increase the degree of engraftment of cardiovascular progenitors and, thus, their potential therapeutic role.

PI: Beatriz Pelacho

We are developing new therapeutic alternatives based on the application of cell and gene therapy, as well as their combination with bioengineering and nanotechnology strategies to prevent and treat adverse cardiac remodeling induced after myocardial ischemia. 

Prior knowledge of the molecular mechanisms involved in these processes, together with the reparative action of stem cells, will enable the promotion of different strategies for their clinical application.

Objectives:

  • To determine the molecular mechanisms involved in the adverse remodeling that occurs after infarction in order to find new therapeutic targets.
  • To demonstrate the efficacy of controlled release systems for proteins/RNA and/or viral vectors for the treatment of cardiovascular diseases.
  • Develop tissue engineering strategies based on the combination of collagen membranes and allogeneic stem cells.

PI: Ana Pardo

Our research focuses on the functional characterization of lung stem cells in homeostasis and after damage, using both in vivo mouse models and ex vivo organoid models to study lung homeostasis, regeneration and disease.

We seek to understand the contribution of lung stem cells to the maintenance of tissue homeostasis and the pathogenesis of specific lung diseases by analyzing their cellular interactions with other lung cells, as well as the molecular mechanisms involved.

In turn, we are also interested in understanding the pathophysiological mechanisms underlying the onset and progression of chronic lung diseases in order to develop strategies to promote tissue regeneration. Understanding the behavior of lung stem cells in this setting is imperative to develop new therapeutic strategies to regenerate damaged tissue and restore lung architecture. However, given the complex interplay of these mechanisms and cell populations involved in the development of pathology, we believe an integration of all these processes is necessary to understand lung pathogenesis in comparison to the complex cellular physiology of healthy lungs. A comprehensive understanding of pathophysiology will allow a more incisive approach to therapeutics.

Objectives:

  • To define the cellular heterogeneity of lung stem cells and characterize specific subpopulations.
  • To study the contribution of lung stem cells to the maintenance of tissue balance and to analyze whether lung stem cells regulate other cell types in homeostasis and in the context of regeneration and disease.
  • To decipher the molecular mechanisms that govern key cellular interactions between stem cells and other cell types in the lung in homeostasis and after damage.

PIs: Froilán Granero y Ana Pérez

Due to the increase in life expectancy in advanced societies, diseases of the musculoskeletal system are one of the major causes of disability and chronic pain.

They are highly prevalent in the general population and it is estimated that about a quarter of the European population suffers or has suffered from a disease of this type. In total, more than 100 million European citizens suffer from chronic pain of musculoskeletal origin, and this type of disorder gives rise to the highest recorded proportion of temporary disability of any other type of ailment.

Our aim is not only to develop new therapeutic strategies for musculoskeletal diseases but also to advance our understanding of the basic mechanisms of disease. In general, bone tissue presents a good regenerative capacity that is not exempt from complications, the most serious being the appearance of fracture pseudarthrosis.

The mechanisms that result in the appearance of fracture pseudarthrosis are unknown, so prevention or pharmacological treatment is not possible. On the other hand, the absence of joint tissue regeneration or repair mechanisms means that any damage results in a degenerative process leading to osteoarthritis, characterized by the total loss of joint function. Current pharmacological treatments are palliative and do not halt the progression of the disease, so there is a need to develop therapies that halt the progression of joint degeneration and activate tissue repair mechanisms.

For the treatment of these pathologies, we are interested in the therapeutic potential of mesenchymal progenitor cells (MSCs). Our ultimate goal is to develop effective therapies for the treatment of osteoarticular diseases and their complications, through tissue engineering strategies that combine MSCs, biomaterials and growth factors.

Identification of the molecular mechanisms involved in the natural processes of osteoarticular regeneration.

FROM THE LABORATORY TO THE PATIENT

Cutting-edge research

To deepen the potential of stem cells and propose new drugs and therapeutic strategies that will soon reach the clinic, we work in close collaboration with the Cell Therapy Area of the Clínica Universidad de Navarra and other transversal programs of the Cima.


CARDIOPATCH

International project on advanced therapies in regenerative medicine and 3D printing for the treatment of myocardial infarction.


BRAVƎ

European project, led by the Clínica Universidad de Navarra, to create a biological device to support a diseased heart.


Organoids

Generation of miniature organs from stem cells to develop new therapeutic alternatives for the treatment of different diseases.

<p>Fachada del Centro de Investigaci&oacute;n M&eacute;dica Aplicada (CIMA)</p>

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Meet the research team

Scientific activity of the
Regenerative Medicine Research Group