The Madrid Institute of Materials Science (ICMM-CSIC), along with six research centers from as many European countries, today held the inaugural meeting of a joint project that focuses on mechanotransductionthat is, on the ability of human cells and tissues to sense and respond to mechanical stimuli.
This is a pioneering initiative to repair spinal cord injuries through materials science, regenerative medicine and nanotechnology, coordinated by the researcher from ICMM-CSIC, Conchi Serrano. The project Piezo4Spinefunded with 3.5 million euros in the European Union’s Pathfinder call, it will analyze the response of cells and tissues to mechanical stimuli in order to develop new effective therapies in the treatment of spinal cord injuries.
The aim of this work is to investigate the mechanical signaling processes and how they are related to neural tissue functioning in physiological and pathological states.
“Our goal is to try to better understand spinal cord injury and, with this knowledge, provide a therapeutic solution for those injured. We have established two specific targets to which the scientific community has not given enough importance so far: piezo mechanoreceptors and fibroblasts that participate in the response to neural damage”, highlighted Serrano.
The sensitivity of cells
Cells are not only sensitive to chemical and biological stimuli, they also sense mechanics. Precisely, the objective of this work is to investigate these mechanical signaling processes and how they relate to the functioning of neural tissue in physiological and pathological states.
This is pioneering science because, in fact, it wasn’t until just over ten years ago (in 2010) when these mechanical receptors were found in mammalian cells. This discovery was recognized with the Nobel Prize in Physiology or Medicine for Arden Patapoutian, in 2021.
“Patapoutian identified for the first time the protein receptor that is in the cell membrane and is capable of feeling mechanical vibrations and triggering specific cell responses”, comments Serrano.
A little over ten years ago, these mechanical receptors were found in mammalian cells, a discovery later recognized with the Nobel Prize in Physiology.
It is these mechanical receptors, called Piezo, that represent the basis of this innovative work and its most revolutionary point: “We asked ourselves why not use these Piezo and see what implication they have in pathological processes such as spinal cord injury”, highlights the researcher .
Fibroblasts, another therapeutic pillar
In addition to the study of piezoreceptors and their involvement in neural damage, the work proposes a second therapeutic pillar: the development of genetic engineering tools to modulate the fibroblasts that participate in healing processes.
These fibroblasts are one of the most rapidly responding cell types to control and heal the damaged area of the body. However, this activation hinders the natural regeneration of damaged neural tissue, in this case, the spinal cord. Therefore, the Piezo4Spine consortium will work to block these fibroblasts, favoring the body’s own regenerative processes.
“Throughout the project, we are going to develop a three-dimensional matrix by 3D bioprinting loaded with nanovehicles that will deliver active therapies to the injury site”, says Serrano, who is certain that, if successful, “this project will allow access to new knowledge and technologies that may be useful not only for neural regeneration, but also for other pathologies that share therapeutic targets”.
Piezo4Spine has the participation of the National Hospital for Paraplegics (Spain), the Italian Technological Institute (Italy), the University of Coimbra (Portugal), the Catholic University of Louvain (Belgium), the company Black Drop Biodrucker GmbH (Germany) and from the company ACIB GmbH (Austria).
Also participating in the ICMM-CSIC are researchers from the Materials for Medicine and Biotechnology Group (MaMBIO), Puerto Morales and Sabino Veintemillas, as well as Ricardo García, from the Advanced Force Microscopy and Nanolithography Group (ForceTool).
The CSIC team, in addition to coordinating the project, will participate and lead the development of therapeutic nanovehicles and the three-dimensional matrix, the study of Piezo receptors and the evaluation and validation of the proof of concept in cell cultures and in the model. clinical trial of spinal cord injury in rats. The Associated Unit that the CSIC maintains with the Hospital de Paraplegicos de Toledo will provide a clinical perspective and support for the close collaboration between both centers.