Decellularized amniotic membrane Scaffolds improve differentiation of iPSCs to functional hepatocyte‐like cells

Abstract

Human‐induced pluripotent stem cells‐derived hepatocyte‐like cells (hiPSCs‐HLCs) holds considerable promise for future clinical personalized therapy of liver disease. However, the low engraftment of these cells in the damaged liver microenvironment is still an obstacle for potential application. In this study, we explored the effectiveness of decellularized amniotic membrane (dAM) matrices for culturing of iPSCs and promoting their differentiation into HLCs. The DNA content assay and histological evaluation indicated that cellular and nuclear residues were efficiently eliminated and the AM extracellular matrix component was maintained during decelluarization. DAM matrices were developed as three‐dimensional scaffolds and hiPSCs were seeded into these scaffolds in defined induction media. In dAM scaffolds, hiPSCs‐HLCs gradually took a typical shape of hepatocytes (polygonal morphology). HiPSCs‐HLCs that were cultured into dAM scaffolds showed a higher level of hepatic markers than those cultured in tissue culture plates (TCPs). Moreover, functional activities in term of albumin and urea synthesis and CYP3A activity were significantly higher in dAM scaffolds than TCPs over the same differentiation period. Thus, based on our results, dAM scaffold might have a considerable potential in liver tissue engineering, because it can improve hepatic differentiation of hiPSCs which exhibited higher level of the hepatic marker and more stable metabolic functions.

Immunomodulatory Properties of Amniotic Membrane Derivatives and Their Potential in Regenerative Medicine

“…It has been successfully used for peripheral nerve regeneration [36], neural differentiation [37], cartilage regeneration [38], as well as substrate for neo-vascularization development [39] and encapsulation. The extracellular matrix (ECM) of hAM is very similar to many other tissues of the body and the decellularization process does not alter its composition [40]. It is made of glycoproteins such as laminin, fibronectin, vitronectin, and nidogen, as well as a collagen types I, III, IV, V, and VI [41].…”

Cell reprogramming in liver with potential clinical correlations

“…To promote the differentiation and maturation of iPSC‐derived hepatocytes, new technologies have been employed to facilitate the hepatic differentiation of iPSC. The decellularized scaffold was the first to be used for the differentiation of iPSC‐derived hepatocytes; decellularized porcine liver scaffold, 11 decellularized Wharton ' s jelly scaffold 12 and decellularized amniotic membrane scaffold 13 have been proven to be ideal models. Regarding 3D bioprinting, it is believed that ink is the key factor.…”

Induced Pluripotent Stem Cells for the Treatment of Liver Diseases: Novel Concepts

“…They demonstrate that decellularized liver scaffold improves differentiation of hiPSCs into HLCs [Lorvellec et al, 2017]. Abazari et al [2020] explored the effectiveness of decellularized amniotic membrane matrices for culturing of iPSCs and promoting their differentiation into HLCs. They found decellularized amniotic membrane scaffold might have a considerable potential in liver tissue engineering, because it can improve hepatic differentiation of hiPSCs which exhibited a higher level of the hepatic marker and more stable metabolic functions.…”