Chemotactic TEG3 Cells' Guiding Platforms Based on PLA Fibers Functionalized With the SDF-1α/CXCL12 Chemokine for Neural Regeneration Therapy.

Oscar Castaño,José Antonio Del Rio,Elisabeth Engel,Andreu Matamoros-Angles,Diego Reginensi,Ana López-Mengual

doi:10.3389/fbioe.2021.627805

Abstract

(Following spinal cord injury, olfactory ensheathing cell (OEC) transplantation is a promising therapeutic approach in promoting functional improvement. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical concentration differences. Here we compare the attachment, morphology, and directionality of an OEC-derived cell line, TEG3 cells, seeded on functionalized nanoscale meshes of Poly(l/dl-lactic acid; PLA) nanofibers. The size of the nanofibers has a strong effect on TEG3 cell adhesion and migration, with the PLA nanofibers having a 950 nm diameter being the ones that show the best results. TEG3 cells are capable of adopting a bipolar morphology on 950 nm fiber surfaces, as well as a highly dynamic behavior in migratory terms. Finally, we observe that functionalized nanofibers, with a chemical concentration increment of SDF-1α/CXCL12, strongly enhance the migratory characteristics of TEG3 cells over inhibitory substrates.

Highlights

Traumatic injuries to the central nervous system (CNS) are associated with the loss, in most cases, of crucial physiological functions
We determined the presence of focal adhesions (FAs; vinculin-positive) on the laminin-coated substrate
As described in other studies (Aguzzi et al, 2013; Reginensi et al, 2015), we observed the presence of two phenotype subpopulations of cultured OECTEG3 cells: bipolar morphology [Schwann cell-like Olfactory ensheathing cells (OECs)], and flattened morphology [astrocytelike OEC] with planar stellate morphology

Summary

Introduction

Traumatic injuries to the central nervous system (CNS) are associated with the loss, in most cases, of crucial physiological functions. Spinal cord injury (SCI) is, a prime example, since it substantially affects the quality of life through loss of function (paralysis and anesthesia) and development of pain and secondary disabilities. Many biological limitations restrict the efficacy of current SCI repair strategies, and many of the regenerative mechanisms are impaired in patients. Olfactory ensheathing cells (OECs) play a key role in the guidance of olfactory axons by trophic and physical support (Kafitz and Greer, 1999; Sonigra et al, 1999). These properties have led to their implementation in several cell therapeutical approaches in the damaged CNS. Evidence of anatomical regeneration (Ramón-Cueto and Nieto-Sampedro, 1994; Li et al, 1997; Imaizumi et al, 2000; Nash et al, 2002) and functional improvement (Li et al, 1997; Ramón-Cueto et al, 1998, 2000; Lu et al, 2001, 2002; López-Vales et al, 2007) has been observed in a variety of SCI models, including in hemisection and in complete transection of the spinal cord

Methods

Results

Discussion

Conclusion