Decellularized Human Liver Extracellular Matrix (hDLM) Mediated Hepatic Differentiation of Human Induced Pluripotent Stem Cells (hIPSc)

Abstract Liver tissue engineering has emerged as a promising approach in organ transplantation, but has been hampered by the lack of a reliable and readily available cell source. Induced pluripotent cells (hiPSC) have been highlighted a desirable source, due to their differentiation potential, ability to self‐renew and the possibility of making patient specific cells. We developed a decellularization protocol that efficiently removes cellular material, while retaining extracellular matrix components. Subsequently, hiPSC were differentiated on the decellularized human liver matrix (hDLM) scaffolds using an established hepatic differentiation protocol. We demonstrate that using hDLM leads to upregulation of functional hepatic markers when compared to standard differentiation conditions. In addition, expression of a number of hepatic transcription and nuclear factors were found to be within levels comparable to those of primary human adult hepatocytes. Analysis of progression of differentiation on hDLM demonstrated that hepatic developmental marker expression was consistent with hepatic development. The hDLM‐derived cells exhibited key hepatic characteristics that were comparable to those observed in primary neonatal human hepatocytes. We investigated the optimal timing of introduction of hDLM into the differentiation protocol, and found that best results are obtained when cells are plated on hDLM since the earliest stages, and accompanied by a progressive loss of sensitivit...
Source: Journal of Tissue Engineering and Regenerative Medicine - Category: Biotechnology Authors: Tags: RESEARCH ARTICLE Source Type: research