Organoid

Organoids represent an advanced tool in cell biology and have redefined biomedical research. Organoids are ideal for studies of biological processes, pharmacological studies, and therapeutic research to imitate pathological processes and preserve genetic integrity. The endoplasmic reticulum (ER) is the central organelle responsible for protein folding, post-translational adaptations, and membrane and luminal protein transportation. ER stress is a disorder influenced by a range of physiological and pathological causes, such as nutrient deficiency, impaired glycosylation, calcium depletion, oxidative stress, DNA damage, and energy disruption. Disturbance of the ER environment triggers aggregation of unfolded/misfolded proteins, accelerating ER stress. The unfolded protein response (UPR) is a transduction mechanism that activates cells in response to ER stress to restore ER homeostasis, altering cancer development and progression. However, the mechanisms through which sustained and unr...

The knowledge about enteric viral infection has vastly increased over the last eight years due to the development of intestinal organoids and enteroids that suppose a step forward from conventional studies using cell lines. Intestinal organoids and enteroids are three-dimensional (3D) models that closely mimic intestinal cellular heterogeneity and organization. The barrier function within these models has been adapted to facilitate viral studies. In this review, several adaptations (such as organoid-derived two-dimensional (2D) monolayers) and original intestinal 3D models are discussed. The specific advantages and applications, as well as improvements of each model are analyzed and an insight into the possible path for the field is given.

Traditional 2D cell cultures do not accurately recapitulate tumor heterogeneity, and insufficient human cell lines are available. Patient-derived xenograft (PDX) models more closely mimic clinical tumor heterogeneity, but are not useful for high-throughput drug screening. Recently, patient-derived organoid cultures have emerged as a novel technique to fill this critical need. Organoids maintain tumor tissue heterogeneity and drug-resistance responses, and thus are useful for high-throughput drug screening. Among various biological tissues used to produce organoid cultures, circulating tumor cells (CTCs) are promising, due to relative ease of ascertainment. CTC-derived organoids could help to acquire relevant genetic and epigenetic information about tumors in real time, and screen and test promising drugs. This could reduce the need for tissue biopsies, which are painful and may be difficult depending on the tumor location. In this review, we have focused on advances in CTC isolation...

In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell–cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue–tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and...

Current knowledge of normal developmental physiology and identification of specific cell types of the kidney at molecular levels enables us to generate various cells of the kidney. The generation of renal specialized cells in vitro with its correct molecular and functional implications is the urgent need for cellular therapy in chronic kidney diseases and for organ formation. Glomerular podocytes are one of the major renal cells lose its functionality to maintain glomerular blood filtration function. In vitro, many inductions or reprogramming methods have been established for podocytes development. In these methods transcription factors, small molecules, and growth factors play the major role to remodel stem cells into podocyte progenitors and towards mature podocytes. Micro ribonucleic acids (miRNAs) have been utilizing as another strategy to generate podocyte. In this review, current protocols for in vitro glomerular podocyte differentiation have summarized emphasizing programming methods, signaling modulation, and cytoskeletal changes. Novel ideas are also pointed out, which are required for efficient optimal glomerular podocyte generation and their functional characterization in vitro with nanoarchitecture impression of the glomerular basement membrane.

The achievement of an HIV cure is dependent on the eradication or permanent silencing of HIV-latent viral reservoirs, including the understudied central nervous system (CNS) reservoir. This requires a deep understanding of the molecular mechanisms of HIV’s entry into the CNS, latency establishment, persistence, and reversal. Therefore, representative CNS culture models that reflect the intercellular dynamics and pathophysiology of the human brain are urgently needed in order to study the CNS viral reservoir and HIV-induced neuropathogenesis. In this study, we characterized a human cerebral organoid model in which microglia grow intrinsically as a CNS culture model to study HIV infection in the CNS. We demonstrated that both cerebral organoids and isolated organoid-derived microglia (oMG), infected with replication-competent HIVbal reporter viruses, support productive HIV infection via the CCR5 co-receptor. Productive HIV infection was only observed in microglial cells. Fluorescence ...

Background. Kidney organoids have been broadly obtained from commercially available induced pluripotent stem cells (iPSCs); however, it has been a great challenge to efficiently produce renal organoid models from patients with autosomal dominant polycystic kidney disease (ADPKD) that recapitulate both embryogenesis and the mechanisms of cystogenesis.Methods. Blood erythroid progenitors (EPs) from two ADPKD patients and one healthy control (HC) donor were reprogrammed by an episomal vector into iPSCs, which were differentiated into renal tubular organoids and then stimulated by forskolin to induce cysts formation. Results. iPSCs derived from EPs exhibited all characteristics of pluripotency and were able to differentiate into all three germ layers. 3D tubular organoids were generated from single cells after 28 days in Matrigel. HC and ADPKD organoids did not spontaneously form cysts, but upon forskolin stimulation, cysts-like structures were observed in the ADPKD organoids but not in...

Current knowledge of normal developmental physiology and identification of specific cell types of the kidney at molecular levels enables us to generate various cells of the kidney. The generation of renal specialized cells in vitro with its correct molecular and functional implications is the urgent need for cellular therapy in chronic kidney diseases and for organ formation. Glomerular podocytes are one of the major renal cells lose its functionality to maintain glomerular blood filtration function. In vitro, many inductions or reprogramming methods have been established for podocytes development. In these methods transcription factors, small molecules, and growth factors play the major role to remodel stem cells into podocyte progenitors and towards mature podocytes. Micro ribonucleic acids (miRNAs) have been utilizing as another strategy to generate podocyte. In this review, current protocols for in vitro glomerular podocyte differentiation have summarized emphasizing programming...