Dynamic behaviors of astrocytes in chemically modified fibrin and collagen hydrogels

Abstract

Astrocytes play a critical role in supporting the normal physiological function of neurons in the central nervous system (CNS). Astrocyte transplantation can potentially promote axonal regeneration and functional recovery after spinal cord injury (SCI). Fibrin and collagen hydrogels provide a growth-permissive substrate and serve as carriers for therapeutic cell transplantation into an injured spinal cord. However, the application of fibrin and collagen may be limited due to its relatively rapid degradation rate in vivo. In this study, immature astrocytes isolated from neonatal rats were grown into fibrin hydrogel containing aprotinin and collagen hydrogel crosslinked with poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-StarPEG), and the cell behavior in these hydrogels was studied. The cell viability of astrocytes in the hydrogels was tested using the LIVE/DEAD® assay and the AlamarBlue® assay, and this study showed that astrocytes maintained good viability in these hydrogels. The cell migration study showed that astrocytes migrated in the fibrin and collagen hydrogels, and the migration speed is similar in these hydrogels. The crosslinking of collagen hydrogel with 4S-StarPEG did not change the astrocyte migration speed. However, the addition of aprotinin in the fibrin hydrogel inhibited astrocyte migration. The expression of chondroitin sulfate proteoglycan (CSPG), including NG2, neurocan, and versican, by astrocytes grown in the hydrogels was analyzed by quantitative RT-PCR. The expression of NG2, neurocan, and versican by the cells in these hydrogels was not significantly different.

Regulation of endothelial cell arrangements within hMSC – HUVEC co-cultured aggregates

“…2]. This phenomenon has been observed previously with other cell types [48], [49]. It is theorised that the density gradient between the aggregates and the encapsulating collagen here encouraged the initial outgrowth.…”

Biomaterial-Supported Cell Transplantation Treatments for Spinal Cord Injury: Challenges and Perspectives

“…Various types of biomaterials have been explored in tissue engineering for SCI repair (Table 1 ). Crosslinking of hydrogels typically increases the overall long-term stability of biomaterials, however this also increases the stiffness and the balance between stiffness and stability is a delicate one for cell adhesion, migration and neuroregenerative work (Khaing et al, 2011 ; Seyedhassantehrani et al, 2016 ). Additionally, surface modification with extracellular matrix (ECM) components, e.g., laminin and fibronectin, or synthetic peptides represents another way to improve cell adhesion and survival by generating a less hostile molecular microenvironment within the biomaterial (Miller et al, 2001 ; Chen et al, 2009 ).…”

Bioinformatics Genes and Pathway Analysis for Chronic Neuropathic Pain after Spinal Cord Injury

“…There are annually 0.25–0.5 million SCI cases around the world and more than 90% are due to traumatic injury [ 19 ]. SCI results in cell loss, disruption of neural circuitry, and chronic functional impairment [ 20 ]; thus patients with chronic NP after SCI may benefit from strategies aiming to promote neurogenesis, neural plasticity, and functional recovery such as human umbilical cord-derived mesenchymal stem cell transplantation [ 21 ], astrocyte transplantation [ 22 – 25 ], and neural stem cell transplantation [ 26 , 27 ]. The mechanisms underlying SCI induced chronic NP remain elusive, and recent advance in neuroscience has implicated that SCI is a polygenic disease and its pathogenic mechanism is associated with changes of gene expression; therefore identification of related genes in chronic NP after SCI could provide new insights into gene function as well as potential diagnostic and therapeutic targets.…”