Decellularized Wharton's jelly extracellular matrix as a promising scaffold for promoting hepatic differentiation of human induced pluripotent stem cells

Abstract

Liver tissue engineering as a therapeutic option for restoring of damaged liver function has a special focus on using native decellularized liver matrix, but there are limitations such as the shortage of liver donor. Therefore, an appropriate alternative scaffold is needed to circumvent the donor shortage. This study was designed to evaluate hepatic differentiation of human induced pluripotent stem cells (hiPSCs) in decellularized Wharton's jelly (WJ) matrix as an alternative for native liver matrix. WJ matrices were treated with a series of detergents for decellularization. Then hiPSCs were seeded into decellularized WJ scaffold (DWJS) for hepatic differentiation by a defined induction protocol. The DNA quantitative assay and histological evaluation showed that cellular and nuclear materials were efficiently removed and the composition of extracellular matrix was maintained. In DWJS, hiPSCs‐derived hepatocyte‐like cells (hiPSCs‐Heps) efficiently entered into the differentiation phase (G1) and gradually took a polygonal shape, a typical shape of hepatocytes. The expression of hepatic‐associated genes (albumin, TAT, Cytokeratin19, and Cyp7A1), albumin and urea secretion in hiPSCs‐Heps cultured into DWJS was significantly higher than those cultured in the culture plates (2D). Altogether, our results suggest that DWJS could provide a proper microenvironment that efficiently promotes hepatic differentiation of hiPSCs.

Extracellular Matrix From Decellularized Wharton’s Jelly Improves the Behavior of Cells From Degenerated Intervertebral Disc

“…It has been demonstrated that DWJM is able to retain many chemotactic factors and soluble bioactive factors positively affecting cell viability and function (Basiri et al, 2019). Therefore, for these different reasons DWJM has been proposed as potential therapeutic agent in many areas (Jadalannagari et al, 2017;Kehtari et al, 2019;Li et al, 2019). A still unexplored field is represented by the degenerated IVD.…”

“…In particular, the abundance of hyaluronic acid (HA) makes this tissue strongly hydrated, viscous and suitable as potential substitute of NP (Jadalannagari et al, 2017;Bullard et al, 2019). In addition, WJ, being rich in growth factors and cytokines (Penolazzi et al, 2010;Jadalannagari et al, 2017;Najar et al, 2018;Kehtari et al, 2019) is particularly attractive for potential application in tissue engineering (Beiki et al, 2017;Basiri et al, 2019;Li et al, 2019;Walker et al, 2019). In recent years, different methods to decellularize the WJ have been developed and compared, aimed at producing a scaffold able to sustain cell viability and proliferation, and preserve the native ECM microstructure and secretion profile (Stocco et al, 2014;Beiki et al, 2017;Jadalannagari et al, 2017).…”

A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

“…In 2019, Kehtari et al [109] proposed a protocol for obtaining hepatic differentiation of hiPSCs seeded on decellularized Wharton jelly (DWJ) scaffolds as an alternative scaffold for circumventing donor shortage. Cell volume increased significantly after differentiation, showing the typical morphological characteristics of hepatocytes.…”

Improved efficacy of bio‐mineralization of human mesenchymal stem cells on modified PLLA nanofibers coated with bioactive materials via enhanced expression of integrin α2β1

“…5 Biomaterials can be divided into natural compounds including hydroxyapatite (Ha), gelatin, collagen, chitosan, etc. [8][9][10] and synthetic ceramics such as poly-L-lactide acid (PLLA), poly caprolactone (PCL), and poly lactide acid (PLA), etc. [11][12][13][14] The compatibility issue can be avoided by using electrospinning technology, in which the polymeric solutions are transformed into nanofibers by electrostatic forces.…”