Journals
Journal:
BIOMACROMOLECULES
ISSN:
1525-7797
Year:
2022
Vol.:
23
N°:
11
pp.
4629 - 4644
The co-administration of glial cell line-derived neurotrophic factor (GDNF) and mesenchymal stem cells (MSCs) in hydrogels (HGs) has emerged as a powerful strategy to enhance the efficient integration of transplanted cells in Parkinson's disease (PD). This strategy could be improved by controlling the cellular microenvironment and biomolecule release and better mimicking the complex properties of the brain tissue. Here, we develop and characterize a drug delivery system for brain repair where MSCs and GDNF are included in a nanoparticle-modified supramolecular guest-host HA HG. In this system, the nanoparticles act as both carriers for the GDNF and active physical crosslinkers of the HG. The multifunctional HG is mechanically compatible with brain tissue and easily injectable. It also protects GDNF from degradation and achieves its controlled release over time. The cytocompatibility studies show that the developed biomaterial provides a friendly environment for MSCs and presents good compatibility with PC12 cells. Finally, using RNA-sequencing (RNA-seq), we investigated how the three-dimensional (3D) environment, provided by the nanostructured HG, impacted the encapsulated cells. The transcriptome analysis supports the beneficial effect of including MSCs in the nanoreinforced HG. An enhancement in the anti-inflammatory effect of MSCs was observed, as well as a differentiation of the MSCs toward a neuron-like cell type. In summary, the suitable strength, excellent self healing properties, good biocompatibility, and ability to boost MSC regenerative potential make this nanoreinforced HG a good candidate for drug and cell administration to the brain.
National and regional funding
Title:
Combinación de biomateriales 3D y miRNAs para la reparacion cardiaca tras infarto de miocardio
Project reference:
PID2021-125124OB-I00
Principal Investigator:
Elisa Garbayo Atienza, María José Blanco Prieto
Funding organisation:
AGENCIA ESTATAL DE INVESTIGACION
Programme/Call:
2021 AEI Proyectos de Generación del Conocimiento
Starting date:
01/09/2022
Ending date:
31/08/2025
Amount awarded:
290.400,00€
Other Funds:
Fondos FEDER