Oxidative stress and docosahexaenoic acid injury lead to increased necroptosis and ferroptosis in retinal pigment epithelium.

Age-related macular degeneration (AMD) is a complex disease caused by different genetic and environmental risk factors leading to loss of cells in the central part of the retina. Oxidative stress appears to be an important environmental risk factor that contributes to both the initiation and progression of AMD. Retinal pigment epithelium (RPE) plays an important role in regulating oxidative stress in the retina and is one of the main retinal cell types affected in AMD.

Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells.

There is intense worldwide effort in generating kidney organoids from pluripotent stem cells, for research, for disease modelling and, perhaps, for making transplantable organs. Organoids generated from pluripotent stem cells (PSC) possess accurate micro-anatomy, but they lack higher-organization. This is a problem, especially for transplantation, as such organoids will not be able to perform their physiological functions.

Renal engineering: strategies to address the problem of the ureter.

Current techniques for making renal organoids generate tissues that show function when transplanted into a host, but they have no ureter through which urine can drain. There are at least 4 possible strategies for adding a ureter: connecting to ta host ureter; inducing an engineered kidney to make a ureter; making a stem-cell derived ureter; and replacement of only damaged cortex and outer medulla, using remaining host calyces, pelvis and ureter. Here we review progress: local BMP4 can induce a collecting duct tubule to become a ureter; a urothelial tube can be produced directly from pluripotent cells, and connect to the collecting duct system of a renal organoid; it is possible to graft ES cell-derived ureters into host kidney rudiments and see connection, smooth muscle development and spontaneous contraction, but this has not yet been achieved with all components being derived from ES cells.

Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell-Derived Ureteric Bud and Mesenchyme.

Background: There is intense interest in replacing kidneys from stem cells. It is now possible to produce, from embryonic or induced pluripotent stem cells, kidney organoids that represent immature kidneys and display some physiologic functions. However, current techniques have not yet resulted in renal tissue with a ureter, which would be needed for engineered kidneys to be clinically useful.

Human Induced Pluripotent Stem Cell-Derived Definitive Endoderm Bulk Culture and Hepatic Differentiation.

We have developed a method to bulk culture definitive endoderm cells generated from human iPSCs which can be stored and differentiated to hepatocytes. Human iPSC-derived definitive endoderm cells were sorted based on the expression of CXCR4. The sorted cells were able to proliferate for extended periods and can be cryopreserved.

Pluripotent stem cells to hepatocytes, the journey so far.

Over the past several years, there has been substantial progress in the field of regenerative medicine, which has enabled new possibilities for research and clinical application. For example, there are ongoing efforts directed at generating functional hepatocytes from adult-derived pluripotent cells for toxicity screening, generating disease models or, in the longer term, for the treatment of liver failure. In the present review, the authors summarise recent developments in regenerative medicine and pluripotent stem cells, the methods and tissues used for reprogramming and the differentiation of induced pluripotent stem cells (iPSCs) into hepatocyte-like cells.

Polarisation and functional characterisation of hepatocytes derived from human embryonic and mesenchymal stem cells.

Adult hepatocytes are polarised with their apical and basolateral membranes separated from neighbouring cells by tight junction proteins. Although efficient differentiation of pluripotent stem cells to hepatocytes has been achieved, the formation of proper polarisation in these cells has not been thoroughly investigated. In the present study, human embryonic stem cells (hESCs) and human mesenchymal stem cells (hMSCs) were differentiated to hepatocyte-like cells and the derived hepatocytes were characterised for mature hepatocyte markers.

Efficient episomal reprogramming of blood mononuclear cells and differentiation to hepatocytes with functional drug metabolism.

The possibility of converting cells from blood mononuclear cells (MNC) to liver cells provides promising opportunities for the study of diseases and the assessment of new drugs. However, clinical applications have to meet GMP requirements and the methods for generating induced pluripotent cells (iPCs) have to avoid insertional mutagenesis, a possibility when using viral vehicles for the delivery of reprogramming factors. We have developed an efficient non-integration method for reprogramming fresh or frozen blood MNC, maintained in an optimised cytokine cocktail, to generate induced pluripotent cells.

Liver tissue engineering and cell sources: issues and challenges.

Liver diseases are of major concern as they now account for millions of deaths annually. As a result of the increased incidence of liver disease, many patients die on the transplant waiting list, before a donor organ becomes available. To meet the huge demand for donor liver, alternative approaches using liver tissue engineering principles are being actively pursued.

Evaluation of polypropylene hollow-fiber prototype bioreactor for bioartificial liver.

Hepatocytes in high density are a requisite for the functional performance of complex devices such as bioartificial liver (BAL). In addition to high cell number, efficient mass transfer is also a key parameter in such devices. High-density culture of cells and efficient mass transfer can be achieved in BAL with hollow-fiber-based bioreactors.