Transplantation of patient-specific bile duct bioengineered with chemically reprogrammed and microtopographically differentiated cells.

Cholangiopathy is a diverse spectrum of chronic progressive bile duct disorders with limited treatment options and dismal outcomes. Scaffold- and stem cell-based tissue engineering technologies hold great promise for reconstructive surgery and tissue repair. Here, we report a combined application of 3D scaffold fabrication and reprogramming of patient-specific human hepatocytes to produce implantable artificial tissues that imitate the mechanical and biological properties of native bile ducts.

Hepatic patch by stacking patient-specific liver progenitor cell sheets formed on multiscale electrospun fibers promotes regenerative therapy for liver injury.

Recently, use of cell sheets with bio-applicable fabrication materials for transplantation has been an attractive approach for the treatment of patients with liver failure. However, renewable and scalable cell sources for engineered tissue patches remain limited. We previously reported a new type of proliferating bipotent human chemically derived hepatic progenitor cells (hCdHs) developed by small molecule-mediated reprogramming.

Nonintegrating Direct Conversion Using mRNA into Hepatocyte-Like Cells.

Recently, several researchers have reported that direct reprogramming techniques can be used to differentiate fibroblasts into hepatocyte-like cells without a pluripotent intermediate step. However, the use of viral vectors for conversion continues to pose important challenges in terms of genome integration. Herein, we propose a new method of direct conversion without genome integration with potential clinical applications.

Small molecule-mediated reprogramming of human hepatocytes into bipotent progenitor cells.

Background & Aims: Currently, much effort is directed towards the development of new cell sources for clinical therapy using cell fate conversion by small molecules. Direct lineage reprogramming to a progenitor state has been reported in terminally differentiated rodent hepatocytes, yet remains a challenge in human hepatocytes.

Methods: Human hepatocytes were isolated from healthy and diseased donor livers and reprogrammed into progenitor cells by 2 small molecules, A83-01 and CHIR99021 (AC), in the presence of EGF and HGF.

Prolongation of liver-specific function for primary hepatocytes maintenance in 3D printed architectures.

Isolated primary hepatocytes from the liver are very similar to in vivo native liver hepatocytes, but they have the disadvantage of a limited lifespan in 2D culture. Although a sandwich culture and 3D organoids with mesenchymal stem cells (MSCs) as an attractive assistant cell source to extend lifespan can be used, it cannot fully reproduce the in vivo architecture. Moreover, long-term 3D culture leads to cell death because of hypoxic stress.

Simple Maturation of Direct-Converted Hepatocytes Derived from Fibroblasts.

Target cells differentiation techniques from stem cells are developed rapidly. Recently, direct conversion techniques are introduced in various categories. Unlike pluripotent stem cells, this technique enables direct differentiation into the other cell types such as neurons, cardiomyocytes, insulin-producing cells, and hepatocytes without going through the pluripotent stage.