Abstract
A critical shortage of donor livers for treating end-stage liver failure signifies the urgent need for alternative treatment options. Hepatocyte-like cells (HLC) derived from various stem cells represent a promising cell source for hepatocyte transplantation, liver tissue engineering, and development of a bioartificial liver assist device. At present, the protocols of hepatic differentiation of stem cells are optimized based on soluble chemical signals introduced in the culture medium and the HLC produced typically retain an immature phenotype. To promote further hepatic differentiation and maturation, biomaterials can be designed to recapitulate cell–extracellular matrix (ECM) interactions in both 2D and 3D configurations. In this review, we will summarize and compare various 2D and 3D biomaterial systems that have been applied to hepatic differentiation, and highlight their roles in presenting biochemical and physical cues to different stem cell sources.
Highlights
Liver, the largest internal organ in our body, performs many important functions including protein synthesis, detoxification, metabolism and bile secretion
When a specific extracellular matrix (ECM) component binds with integrins that recognize the motifs on the ECM (e.g., α5β1), focal adhesion kinase is activated to mediate downstream signaling to elicit an ECM-specific response on stem cell differentiation [80,81]
The capability of stem cells to differentiate into Hepatocyte-like cells (HLC) is well documented, but producing HLC with a mature hepatocyte phenotype remains a challenge
Summary
The largest internal organ in our body, performs many important functions including protein synthesis, detoxification, metabolism and bile secretion. Hepatocyte-like cells (HLC) differentiated from stem cells, with morphological, phenotypic, and functional characteristics of mature hepatocytes, could potentially be employed in hepatocyte transplantation and liver tissue engineering. Natural or synthetic biomaterials can be employed to present physical and biochemical cues, which serve as additional stimuli to enhance hepatic differentiation of stem cells. While biomaterials such as collagen, laminin and decellularized ECM are traditionally applied as a 2D coating, the development of 3D biomaterial scaffolds has provided an alternative to influence cell fate via supplying ECM cues in 3D. We will discuss how various 2D and 3D biomaterial systems modulate hepatic differentiation of stem cells
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