Engineered Humanized Spinal Cord Construct for Advancing Health and Disease Research

Descripción del proyecto

Médula espinal humana bioimpresa

Para comprender y tratar los trastornos de la médula espinal y las enfermedades neurodegenerativas se necesitan modelos que reflejen con precisión la complejidad de la médula espinal humana, algo que los sistemas actuales no logran. El equipo del proyecto SpineCraft, financiado por el Consejo Europeo de Investigación, desarrollará un modelo funcional en cuatro dimensiones de la médula espinal humana que combine una arquitectura anatómicamente precisa con una organización espacial controlada de las células neuronales y vasculares, utilizando técnicas avanzadas de bioimpresión y matrices extracelulares modificadas genéticamente. Se utilizarán células madre pluripotentes inducidas humanas para generar los tipos celulares necesarios, que se integrarán en una estructura biofidélica predefinida. Las células derivadas de pacientes se incorporarán posteriormente para modelar características específicas de la enfermedad, incluida la esclerosis lateral amiotrófica. La plataforma se validará mediante técnicas de obtención de imágenes, análisis multiómico y electrofisiología, lo que permitirá estudiar la biología de la médula espinal, los mecanismos de las enfermedades y las estrategias terapéuticas.

Objetivo

Current in vitro models of the central nervous system (CNS) fail to recapitulate its intricate structure and function, posing significant challenges to advancing our understanding of neurodevelopmental, neurological, and neurodegenerative diseases. Current 2D cultures, 3D organoids and animal models are limited for studying both healthy and pathological states, slowing progress in neuroscience. New CNS models must integrate advanced biofabrication, innovative bioinks, and cellular engineering to mimic the complex structure, vascular networks, and multi-cellular integration of the CNS.

Recent progress in bioprinting and tissue engineering enable the fabrication of complex structures, while bioinks and biomaterials provide optimal cellular environments for differentiation, and functional integration. Additionally, state-of-the-art imaging and omic technologies have improved the ability to capture detailed structural and cellular data, ensuring that CNS models mimic native CNS architecture and dynamics.

SPINECRAFT will develop a 4D functional human spinal cord construct (hSCC) that replicates the structural complexity and dynamic functionality of the human spinal cord (hSC). Our approach will use advanced imaging and computational techniques to map the architecture and cell distribution of the hSC. Using this information, we will generate human neural and vascular cells alongside bioinks designed to mimic the native microenvironment. We will then print a high-fidelity hSCC, validate it with imaging, multi-omics, and electrophysiology, and integrate patient-specific iPSCs to model amyotrophic lateral sclerosis (ALS) to recapitulate disease-specific microenvironments.

SPINECRAFT represents a paradigm shift in CNS research, providing a versatile platform to study hSC biology, neurodegenerative diseases, and regenerative therapies. This integrative approach will raise the standards of tissue engineering and drive technological advances beyond spinal cord applications.