Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells

Abstract

Hydrogels provide a unique tool for neural tissue engineering. These materials can be customized for certain functions, i.e. to provide cell/drug delivery or act as a physical scaffold. Unfortunately, hydrogel complexities can negatively impact their biocompatibility, resulting in unintended consequences. These adverse effects may be combated with a better understanding of hydrogel chemical, physical, and mechanical properties, and how these properties affect encapsulated neural cells. We defined the polymerization and degradation rates and compressive moduli of 25 hydrogels formulated from different concentrations of hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Changes in compressive modulus were driven primarily by the HA concentration. The in vitro biocompatibility of fetal-derived (fNPC) and adult-derived (aNPC) neural progenitor cells was dependent on hydrogel formulation. Acute survival of fNPC benefited from hydrogel encapsulation. NPC differentiation was divergent: fNPC differentiated into mostly glial cells, compared with neuronal differentiation of aNPC. Differentiation was influenced in part by the hydrogel mechanical properties. This study indicates that there can be a wide range of HA and PEG hydrogels compatible with NPC. Additionally, this is the first study comparing hydrogel encapsulation of NPC derived from different aged sources, with data suggesting that fNPC and aNPC respond dissimilarly within the same hydrogel formulation.

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

“…This concentration was rheologically comparable to uninjured brain tissue, with an elastic modulus of 500–1000 Pa [36–38], which could explain why this concentration was so efficient in attracting host cells, specifically neural progenitors and oligodendrocytes. The mechanical properties of the hydrogel play an important part in cell invasion and phenotypic differentiation [25,26] Stiffer gels (1000–10,000 Pa) are associated with astrocytes, whereas softer gels (100–1000 Pa) are more likely to promote neuronal differentiation [41]. An intermediate stiffness (400–800 Pa) provides a mixtures of cells, as was seen here in the 8 mg/mL condition (460 Pa), and could provide mechanical properties that are conducive to neural tissue engineering requiring neurons, astrocytes, as well as oligodendrocytes.…”

3D in vitro modeling of the central nervous system

“…Additionally, the differentiation pattern was shown to be divergent in case of fetal vs. adult progenitor cells. Fetal cells had the tendency to differentiate into glial cells, and while adult cells preferentially differentiated into neurons (Aurand et al, 2014). However, due to the tendency to inhibit neurite outgrowth HA has not been successful in long-term cultures (Bignami et al, 1993).…”

In vitro bioengineered model of cortical brain tissue

“…These published methods can be divided into three categories: organoids 2,12-14 , neurospheroids 15-17 and hydrogel cultures 1,18,19 .…”

“…The hydrogel cultures are based on uniformly dispersed cells inside in situ gelling biomaterials 1,18,19 , and rely on self-directed assembly of cells over time. Similarly, our protocol utilizes hydrogels as an environment for axonal outgrowth, but at the same time provides compartmentalized neuronal growth to mimic the architecture of the cerebral cortex.…”