Fluid Flow Regulation of Revascularization and Cellular Organization in a Bioengineered Liver Platform

Abstract

Overall, we were able to unveil the potential central role of discrete mechanical stimulation through the NO pathway in the revascularization and cellular organization of a bioengineered liver. Last, we propose that this organ bioengineering platform can contribute significantly to the identification of physiological mechanisms of liver organogenesis and regeneration and improve our ability to bioengineer livers for transplantation.

Vasculature reconstruction of decellularized liver scaffolds via gelatin‐based re‐endothelialization

“…However, one may expect that the endothelial cells lining up the liver scaffold vasculatures would still experience the high shear stress from the abdominal arterial flow. This is relevant as it has shown that high shear stresses negatively influenced the viability of cells within the liver scaffolds . This report may explain the large amount of the caspase‐3+ endothelial cells observed in the re‐endothelialized liver scaffold transplants (Fig.…”

“…A variety of cell types have been examined for liver scaffold recellularization, including immortalized cells, adult primary cells, fetal cells, mesenchymal stem cells and induced pluripotent stem cells . Many studies have shown that recellularized liver scaffolds perform hepatic specific functions in vitro .…”

“…2 The resulting decellularized liver scaffold preserves a threedimensional (3D) matrix architecture that closely mimics the native liver and retains a plethora of matrix-associated proteins as well as endogenous growth factors. [2][3][4][5][6] A variety of cell types have been examined for liver scaffold recellularization, including immortalized cells, 7,8 adult primary cells, 2,6 fetal cells, 9,10 mesenchymal stem cells 11 and induced pluripotent stem cells. 4 Many studies have shown that recellularized liver scaffolds perform hepatic specific functions in vitro.…”

Self‐assembled liver organoids recapitulate hepatobiliary organogenesis in vitro

“…To create human liver organoids, we used our previously described decellularization method to fabricate liver ECM scaffolds and then sectioned the scaffold and seeded sections (8‐mm ECM discs) with hFLPC cultures that contained liver stromal (25%‐40%) and endothelial (5%‐15%) cells (http://onlinelibrary.wiley.com/doi/10.1002/hep.29483/suppinfo). Within 2‐3 weeks postseeding and culture in LDM, the cells and ECM self‐assembled into 3D organoid structures with progressive cellular organization and differentiation (http://onlinelibrary.wiley.com/doi/10.1002/hep.29483/suppinfo).…”

Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells

“…15,34 Interestingly, other vascular mediators generated from liver circulation (eg, prostaglandins, nitric oxide, and catecholamines) could also be involved in hepatic growth and maturation, recently shown in a bioengineered liver. 35 …”