Optimizing fibrin hydrogel toward effective neural progenitor cell delivery in spinal cord injury

Abstract

Transplantation of neural progenitor cell (NPC) possessing the potential to differentiate into neurons may guard against spinal cord injury (SCI)- associated neuronal trauma. We propose that autologous-like NPC may reduce post-transplant immune response. The study used the rat SCI model to prove this concept. For isolation and expansion of rat NPC for cell-based SCI therapy, the in vitro protocol standardized with human NPC seemed suitable. The primary aim of this study is to select a cell/neural tissue-compatible biomaterial for improving NPC survival in vivo. The composition of the fibrin hydrogel is adjusted to obtain degradable, porous, and robust fibrin strands for supporting neural cell attachment, migration, and tissue regeneration. This study employed NPC culture to evaluate the cytocompatibility and suitability of the hydrogel, composed by adding graded concentrations of thrombin to a fixed fibrinogen concentration. The microstructure evaluation by scanning electron microscope guided the selection of a suitable composition for delivering the embedded cells. On adding more thrombin, fibrinogen clotted quickly but reduced porosity, pore size, and fiber strand thickness. The high activity of thrombin also affected NPC morphology and the in vitro cell survival. The selected hydrogel carried viable NPC and retained them at the injury site post-transplantation. The fibrin hydrogel played a protective role throughout the transfer process by providing cell attachment sites and survival signals. The fibrin and NPC together regulated the immune response at the SCI site reducing ED1+ve/ED2+ve macrophages in the early period of 8–16 d after injury. Migration of β-III tubulin+ve neural-like cells into the fibrin-injected control SCI is evident. The continuous use of a non-neurotoxic fibrin matrix could be a convenient strategy for in vitro NPC preparation, minimally invasive cell delivery, and better transplantation outcome.

Neural Tissue Engineering with Rat Adipose-Derived Mesenchymal Stem Cells: The Role of an Injectable, Resorbable Hydrogel Scaffold Derived from Oxidized Alginate and Gelatin

“…Using lineage-committed cells and biomaterials can resolve this issue to a great extent. 70 The protocol we employed for culturing 39,64,68 has been shown to express the functional neuronal marker synaptophysin and the astrocyte marker GFAP was minimum.…”

“…The maintenance of ADMSC properties like proliferation and transdifferentiation might get affected after in vivo transplantation, especially because of the injury site environment. Using lineage-committed cells and biomaterials can resolve this issue to a great extent . The protocol we employed for culturing ,, has been shown to express the functional neuronal marker synaptophysin and the astrocyte marker GFAP was minimum.…”

Structural changes of spinal cord tissue of rats with experimental spinal cord injury after implantation of fibrin matrix associated with neural and mesenchymal progenitor cells

“…gradable hydrogels or glues with a high liquid content and the ability to hold cells after polymerization are formed, promoting adhesion, viability, proliferation and differentiation of cells [15][16][17][18]. It was shown that after implantation of a 3D-aligned fibrin hydrogel in rats with SC hemisection, the reconstruction of nerve fibers and blood vessels at the site of damage occurred (4 weeks), as well as the sprouting of a new axon completely through the damaged area (8 weeks) [8].…”

Research progress of hydrogels as delivery systems and scaffolds in the treatment of secondary spinal cord injury

“…Fibrin is a common raw material for protein-based hydrogels. Sudhadevi et al (2021) synthesized a fibrin hydrogel loaded with neural progenitor cells (NPCs). Fibrin hydrogel is composed of a fibrinogen solution mixed with thrombin.…”