Modeling dry eye with an air-liquid interface in corneal epithelium-on-a-chip.

Dry eye syndrome (DES) is a complex ocular condition characterized by an unstable tear film and inadequate tear production, leading to tissue damage. Despite its common occurrence, there is currently no comprehensive in vitro model that accurately reproduce the cellular characteristics of DES. Here we modified a corneal epithelium-on-a-chip (CEpOC) model to recapitulate DES by subjecting HCE-T human corneal epithelial cells to an air-liquid (AL) interface stimulus.

Cyclic Stretching Enhances Angiocrine Signals at Liver Bud Stage from Human Pluripotent Stem Cells in Two-Dimensional Culture.

Angiocrine signals during the development and growth of organs, including the liver, intestine, lung, and bone, are essential components of intercellular communication. The signals elicited during the liver bud stage are critical for vascularization and enhanced during the intercellular communication between the cells negative for kinase insert domain receptor (KDR) (KDR cells) and the cells positive for KDR (KDR cells), which constitute the liver bud. However, the use of a human pluripotent stem cell (hPSC)-derived system has not facilitated the generation of a perfusable vascularized liver organoid that allows elucidation of liver development and has great potential for liver transplantation.

Emerging platinum(IV) prodrug nanotherapeutics: A new epoch for platinum-based cancer therapy.

Owing to the unique DNA damaging cytotoxicity, platinum (Pt)-based chemotherapy has long been the first-line choice for clinical oncology. Unfortunately, Pt drugs are restricted by the severe dose-dependent toxicity and drug resistance. Correspondingly, Pt(IV) prodrugs are developed with the aim to improve the antitumor performance of Pt drugs.

Critical roles of linker length in determining the chemical and self-assembly stability of SN38 homodimeric nanoprodrugs.

Homodimeric prodrug nanoassemblies (HDPNs) have been widely studied for efficient cancer therapy by virtue of their ultra-high drug loading and distinct nanostructure. However, the development of SN38 HDPNs is still a great challenge due to the rigid planar aromatic ring structure. Improving the structural flexibility of homodimeric prodrugs by increasing the linker length may be a potential strategy for constructing SN38 HDPNs.

Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction.

To clarify the physiological and pathological roles of gut-liver-axis (GLA) in the human body, a GLA microphysiological system (GLA-MPS) holds great potential. However, in current GLA-MPSs, the importance of a physiologically relevant flow for gut and liver cells' cultivation is not fully addressed. In addition, the integration of individual organ perfusion, circulation flow, and organ tissue functions in a single device has not been achieved.

Tumor-on-a-chip model for advancement of anti-cancer nano drug delivery system.

Despite explosive growth in the development of nano-drug delivery systems (NDDS) targeting tumors in the last few decades, clinical translation rates are low owing to the lack of efficient models for evaluating and predicting responses. Microfluidics-based tumor-on-a-chip (TOC) systems provide a promising approach to address these challenges. The integrated engineered platforms can recapitulate complex in vivo tumor features at a microscale level, such as the tumor microenvironment, three-dimensional tissue structure, and dynamic culture conditions, thus improving the correlation between results derived from preclinical and clinical trials in evaluating anticancer nanomedicines.

An efficient simplified method for the generation of corneal epithelial cells from human pluripotent stem cells.

Corneal epithelial cells derived from human pluripotent stem cells (hPSCs) are an important cell source for preclinical models to test ophthalmic drugs. However, current differentiation protocols lack instructions regarding optimal culturing conditions, which hinders the quality of cells and limits scale-up. Here, we introduce a simplified small molecule-based corneal induction method (SSM-CI) to generate corneal epithelial cells from hPSCs.

In vitro culture at 39 °C during hepatic maturation of human ES cells facilitates hepatocyte-like cell functions.

Hepatocyte-like cells derived from human pluripotent stem cells (hPSC-HLCs) offer an alternative to primary hepatocytes commonly used for drug screenings and toxicological tests. However, these cells do not have hepatic functions comparable to those of hepatocytes in vivo due to insufficient hepatic differentiation. Here we showed that the hepatic functions of hPSC-HLCs were facilitated by applying physiological liver temperatures during hepatic differentiation.

Generation and Gene Expression Profiles of Grevy's Zebra Induced Pluripotent Stem Cells.

Induced pluripotent stem cells (iPSCs) can serve as a biological resource for functional and conservation research for various species. This realization has led to the generation of iPSCs from many species, including those identified as endangered. However, the understanding of species variation in mammalian iPSCs remains largely unknown.

Nanocasting of fibrous morphology on a substrate for long-term propagation of human induced pluripotent stem cells.

Human-induced pluripotent stem cells (hiPSCs) can be self-renewed for many generations on nanofibrous substrates. Herein, a casting method is developed to replicate the nanofibrous morphology into a thin layer of polymethylsiloxane (PDMS). The template is obtained by electrospinning and chemical crosslinking of gelatin nanofibers on a glass slide.

Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration.

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling, including an acute and transient breakdown of collagen that produces gelatin. Although the physiological function of this process is unclear, it has inspired the application of gelatin to injured skeletal muscle for a potential pro-regenerative effect. Here, we investigated a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by the hormetic effects of reactive oxygen species (ROS).

Triglyceride-Mimetic Structure-Gated Prodrug Nanoparticles for Smart Cancer Therapy.

Off-target drug release and insufficient drug delivery are the main obstacles for effective anticancer chemotherapy. Prodrug-based self-assembled nanoparticles bioactivated under tumor-specific conditions are one of the effective strategies to achieve on-demand drug release and effective tumor accumulation. Herein, stimuli-activable prodrugs are designed yielding smart tumor delivery by combination of the triglyceride-mimic (TG-mimetic) prodrug structure and disulfide bond.

Spatiotemporal determination of metabolite activities in the corneal epithelium on a chip.

The corneal epithelial barrier maintains the metabolic activities of the ocular surface by regulating membrane transporters and metabolic enzymes responsible for the homeostasis of the eye as well as the pharmacokinetic behavior of drugs. Despite its importance, no established biomimetic in vitro methods are available to perform the spatiotemporal investigation of metabolism and determine the transportation of endogenous and exogenous molecules across the corneal epithelium barrier. This study introduces multiple corneal epitheliums on a chip namely, Corneal Epithelium on a Chip (CEpOC), which enables the spatiotemporal collection as well as analysis of micro-scaled extracellular metabolites from both the apical and basolateral sides of the barriers.

Evaluation of the Effects of Solvents Used in the Fabrication of Microfluidic Devices on Cell Cultures.

Microfluidic microphysiological systems (MPSs) or "organs-on-a-chip" are a promising alternative to animal models for drug screening and toxicology tests. However, most microfluidic devices employ polydimethylsiloxane (PDMS) as the structural material; and this has several drawbacks. Cyclo-olefin polymers (COPs) are more advantageous than PDMS and other thermoplastic materials because of their low drug absorption and autofluorescence.

Cyclo olefin polymer-based solvent-free mass-productive microphysiological systems.

A microphysiological system (MPS) holds great promise for drug screening and toxicological testing as an alternative to animal models. However, this platform faces several challenges in terms of the materials used (e.g.

Untargeted LC-MS Metabolomics for the Analysis of Micro-scaled Extracellular Metabolites from Hepatocytes.

Metabolome analysis in micro physiological models is a challenge due to the low volume of the cell culture medium (CCM). Here, we report a LC-MS-based untargeted metabolomics protocol for the detection of hepatocyte extracellular metabolites from micro-scale samples of CCM. Using a single LC-MS method we have detected 57 metabolites of which 27 showed >2-fold shifts after 72-hour incubation.

Terahertz pulse-altered gene networks in human induced pluripotent stem cells.

Terahertz (THz) irradiation has been exploited in biomedical applications involving non-invasive manipulation of living cells. We developed an apparatus for studying the effects of THz pulse irradiation on living human induced pluripotent stem cells. The THz pulse of the maximum electric field reached 0.

Recapitulation of Human Embryonic Heartbeat to Promote Differentiation of Hepatic Endoderm to Hepatoblasts.

Hepatic development requires multiple sequential physicochemical environmental changes in an embryo, and human pluripotent stem cells (hPSCs) allow for the elucidation of this embryonic developmental process. However, the current methods for hPSC-hepatic differentiation, which employ various biochemical substances, produce hPSC-derived hepatocytes with less functionality than primary hepatocytes, due to a lack of physical stimuli, such as heart beating. Here, we developed a microfluidic platform that recapitulates the beating of a human embryonic heart to improve the functionality of hepatoblasts derived from hepatic endoderm (HE) .

Genetic Signatures of Evolution of the Pluripotency Gene Regulating Network across Mammals.

Mammalian pluripotent stem cells (PSCs) have distinct molecular and biological characteristics among species, but to date we lack a comprehensive understanding of regulatory network evolution in mammals. Here, we carried out a comparative genetic analysis of 134 genes constituting the pluripotency gene regulatory network across 48 mammalian species covering all the major taxonomic groups. We report that mammalian genes in the pluripotency regulatory network show a remarkably high degree of evolutionary stasis, suggesting the conservation of fundamental biological process of mammalian PSCs across species.