Bioengineering vascularized liver tissue for biomedical research and application.

The liver performs a wide range of biological functions that are essential to body homeostasis. Damage to liver tissue can result in reduced organ function, and if chronic in nature can lead to organ scarring and progressive disease. Currently, donor liver transplantation is the only longterm treatment for end-stage liver disease. However, orthotopic organ transplantation suffers from several drawbacks that include organ scarcity and lifelong immunosuppression. Therefore, new therapeutic strategies are required. One promising strategy is the engineering of implantable and vascularized liver tissue. This resource could also be used to build the next generation of liver tissue models to better understand human health, disease and aging in vitro. This article reviews recent progress in the field of liver tissue bioengineering, including microfluidic-based systems, bio-printed vascularized tissue, liver spheroids and organoid models, and the induction of angiogenesis in vivo.

Effects of spike proteins on angiotensin converting enzyme 2 (ACE2).

The Coronavirus Disease 2019 (COVID-19) pandemic was caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enters host cells through interactions of its spike protein to Angiotensin-Converting Enzyme 2 (ACE2). ACE2 is a peptidase that cleaves Angiotensin II, a critical pathological mediator. This study investigated if the spike protein binding to ACE2 compromises its peptidase activity. Spike/ACE2 Binding Assays suggested that spike proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, but not HKU1, bind to ACE2. S1 and receptor-binding domain (RBD), but not S2, extracellular domain (ECD) or CendR domain, bind to ACE2. While glycosylated spike proteins prepared in HEK293 cells bind to ACE2, non-glycosylated proteins produced in E. coli do not. Cysteine residues of the spike protein expressed in HEK293 cells are fully oxidized, while those of the protein expressed in E. coli are reduced. The deglycosylation of HEK cell-produced protein attenuates the ACE2 binding, while the oxidation of the E. coli protein does not promote the binding. The S1 protein of SARS-CoV-2 enhances the ACE2 peptidase activity, while SARS-CoV, MERS-CoV or HKU1 does not. The ACE2 activity is enhanced by RBD, but not ECD or CendR. In contrast to distinct ACE2 binding capacities of proteins expressed in HEK293 cells and in E. coli, spike proteins expressed in both systems enhance the ACE2 activity. Thus, the spike protein of SARS-CoV-2, but not other coronaviruses, enhances the ACE2 peptidase activity through its RBD in a glycosylation-independent manner.

Natural Scaffolds Used for Liver Regeneration: A Narrative Update.

Annually chronic liver diseases cause two million death worldwide. Although liver transplantation (LT) is still considered the best therapeutic option, the limited number of donated livers and lifelong side effects of LT has led researchers to seek alternative therapies. Tissue engineering (TE) as a promising method is considered for liver repair and regeneration. TE uses natural or synthetic scaffolds, functional somatic cells, multipotent stem cells, and growth factors to develop new organs. Biological scaffolds are notable in TE because of their capacity to mimic extracellular matrices, biodegradability, and biocompatibility. Moreover, natural scaffolds are classified based on their source and function in three separate groups. Hemostat-based scaffolds as the first group were reviewed for their application in coagulation in liver injury or surgery. Furthermore, recent studies showed improvement in the function of biological hydrogels in liver regeneration and vascularity. In addition, different applications of natural scaffolds were discussed and compared with synthetic scaffolds. Finally, we focused on the efforts to improve the performance of decellularized extracellular matrixes for liver implantation.