Generation of Transplantable Three-Dimensional Hepatic-Patch to Improve the Functionality of Hepatic Cells In Vitro and In Vivo

Abstract

Cell therapy and tissue engineering (TE) are considered alternative therapeutic approaches to organ transplantation. Since cell therapy approaches achieved little success for liver failure treatment, liver TE is considered a more promising alternative. In this study, we produced a liver tissue equivalent (called ''liver-derived extracellular matrix scaffold [LEMS]-Patch'') by co-culture of human bone marrow stromal cells, human umbilical vein endothelial cells, and a hepatoma cell line, Huh7, within an artificial three-dimensional liverextracellular matrix scaffold. The results showed significant increase in the liver-specific gene expression and hepatic functions, in terms of albumin (ALB) and fibrinogen secretion, urea production, and cytochrome inducibility in the LEMS-Patch compared to controls. In addition, transplanted LEMS-Patch was successfully incorporated into the recipient liver of acute liver failure mice and produced human ALB. Consequently, our data demonstrated that the generated LEMS-Patch could be used as a good platform for functional improvement of hepatic cells in vitro and in vivo.

Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells

“…MSCs were used in present work owing to the potential capabilities to provide more clinically important evidence from our studies. It was previously described that MSCs seeding on the scaffold materials had less spread and more proliferation and differentiation rate than MSCs on defect area without scaffold [33][34][35]. Hence, the results presented that concurrent use of the fabricated scaffold and cell is capable to improve histological parameters in bone defect areas.…”

Tissue-Specific Microparticles Improve Organoid Microenvironment for Efficient Maturation of Pluripotent Stem-Cell-Derived Hepatocytes

“…Studies have demonstrated that ECM hydrogels derived from different organs, such as heart [ 48 , 49 ], liver [ 54 ], skeletal muscles, and kidney [ 51 ], could serve as a proper cell culture platform to improve cell functionality and maturity. In our previous studies, liver ECM was used as a hydrogel [ 21 ] and patch [ 22 ] to improve the functionality of hepatic cells. The reconstruction of an ECM in a 3D culture of microscale cell spheroids is a challenging subject.…”

“…Recent studies on decellularized liver tissue unveiled the role of liver ECM in activating hepatic differentiation and endodermal organoid formation [16][17][18][19]. Some studies have demonstrated that liver ECM promotes the maturation of human PSC-derived hepatocytes by downregulation of fetal liver markers (AFP and CYP3A7) and upregulation of other CYP genes as markers of metabolic activity [20][21][22]. Hence, an innovative strategy to establish liver organoids benefiting from both similar size and cell-ECM interactions is urgently required.…”

Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

“…These forms are fabricated using digested ECM, homogenized ECM, or ECM ink, respectively. These ECM forms could be used for cell delivery, but they have relevant limitations, mainly due to the additional loss of biochemical components during the digestion and fabrication processes [97,[109][110][111][112][113][114][115][116].…”