Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel

Abstract

Bioengineers have designed numerous instructive brain extracellular matrix (ECM) environments with tailored and tunable protein compositions and biomechanical properties in vitro to study astrocyte reactivity during trauma and inflammation. However, a major limitation of both protein‐based and synthetic model microenvironments is that astrocytes within fail to retain their characteristic stellate morphology and quiescent state without becoming activated under “normal” culture conditions. Here, a synthetic hydrogel is introduced, which for the first time demonstrates maintenance of astrocyte quiescence and activation on demand. With this synthetic brain hydrogel, the brain‐specific integrin‐binding and matrix metalloprotease‐degradable domains of proteins are shown to control astrocyte star‐shaped morphologies, and an ECM condition that maintains astrocyte quiescence with minimal activation can be achieved. In addition, activation can be induced in a dose‐dependent manner via both defined cytokine cocktails and low molecular weight hyaluronic acid. This synthetic brain hydrogel is envisioned as a new tool to study the physiological role of astrocytes in health and disease.

Modeling the effects of hyaluronic acid degradation on the regulation of human astrocyte phenotype using multicomponent interpenetrating polymer networks (mIPNs)

“…As expected the distribution in the round control group was shifted toward the left of the figure indicating low levels of cell spreading and round morphologies. The measured cell dimensions are in close agreement and within the range of recently published results for the morphological characterization of human astrocytes in the PEG based hydrogels 49 .

Figure 3 Average total processes length ( A ), average number of endpoints ( B ), Total processes length distribution ( C ) and number of endpoint distribution ( D ).

…”

Conventional immunomarkers stain a fraction of astrocytes in vitro: A comparison of rat cortical and spinal cord astrocytes in naïve and stimulated cultures

“…Astrocytes cultured in a 3D hydrogel environment are less reactive than in 2D culture and exhibit morphologies similar to astrocytes in vivo (Balasubramanian et al., 2016; East et al., 2009; Frampton et al., 2011; Placone et al., 2015). Recently, a peptide hydrogel engineered to mimic the brain extracellular matrix was found to maintain astrocyte quiescence and minimize activation (Galarza et al., 2020). An astrocyte marker that is not affected by activation state will be useful moving forward to study astrocyte behavior in biomaterial‐based culture systems.…”

Biomaterial-supported MSC transplantation enhances cell–cell communication for spinal cord injury

“…For example, Liu et al were the first to demonstrate that intravenous injection of MSC-derived exosome after SCI leads to a decreased number of C3 + /GFAP + astrocytes in the damaged region in acute period. They ascribe these results to the secretion of TSG-6 by MSCs and consequently decreased NF-κB signaling, which induces А1 neuroinflammatory reactive astrocytes [103,104]. Studies designed to estimate the efficacy of MSCs is intended for neuroregeneration in SCI concentrate on the state of reactive astrocytes and extracellular matrix in the glial scar.…”