Engineering human immune organoids for translational immunology.

Animal models have been extensively used as a gold standard in various biological research, including immunological studies. Despite high availability and ease of handling procedure, they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures. Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs.

Extracellularly Detectable Electrochemical Signals of Living Cells Originate from Metabolic Reactions.

Direct detection of cellular redox signals has shown immense potential as a novel living cell analysis tool. However, the origin of such signals remains unknown, which hinders the widespread use of electrochemical methods for cellular research. In this study, the authors found that intracellular metabolic pathways that generate adenosine triphosphate (ATP) are the main contributors to extracellularly detectable electrochemical signals.

In Situ Detection of Kidney Organoid Generation From Stem Cells Using a Simple Electrochemical Method.

Organoids that mimic the structural and cellular characteristics of kidneys in vitro have recently emerged as a promising source for biomedical research. However, uncontrollable cellular heterogeneity after differentiation often results in the generation of off-target cells, one of the most challenging issues in organoid research. This study proposes a new method that enables the real-time assessment of kidney organoids derived from stem cells.

Single metal-organic framework-embedded nanopit arrays: A new way to control neural stem cell differentiation.

Stable and continuous supply of essential biomolecules is critical to mimic in vivo microenvironments wherein spontaneous generation of various cell types occurs. Here, we report a new platform that enables highly efficient neuronal cell generation of neural stem cells using single metal-organic framework (MOF) nanoparticle-embedded nanopit arrays (SMENA). By optimizing the physical parameters of homogeneous periodic nanopatterns, each nanopit can confine single nMOFs (UiO-67) that are specifically designed for long-term storage and release of retinoic acid (RA).

Raman Spectroscopy-Based 3D Analysis of Odontogenic Differentiation of Human Dental Pulp Stem Cell Spheroids.

Numerous efforts have been made to establish three-dimensional (3D) cell cultures that mimic the structure, cell composition, and functions of actual tissues and organs ; however, owing to its intrinsic complexity, precise characterization of 3D differentiation remains challenging and often results in high variations in the resulting differentiated spheroids. This study reports a 3D Raman mapping-based analytical method that helps us to identify the crucial factors responsible for inducing variability in differentiated stem cell spheroids. Human dental pulp stem cell spheroids were generated at various cell densities using the hanging drop (HD) and molded parafilm-based (MP) methods and were then further subjected to odontogenic differentiation.

Autofluorescence-Raman Mapping Integration analysis for ultra-fast label-free monitoring of adipogenic differentiation of stem cells.

Stem cell-based therapies have recently emerged to treat various incurable diseases and disorders. Types of stem cell-derived cells and their functions should be intensively analyzed before therapy. However, current pre-treatment steps for biological analysis are mostly destructive.

Recent Advances in Electrochemical Sensors for the Detection of Biomolecules and Whole Cells.

Electrochemical sensors are considered an auspicious tool to detect biomolecules (e.g., DNA, proteins, and lipids), which are valuable sources for the early diagnosis of diseases and disorders.

A Spheroid-Forming Hybrid Gold Nanostructure Platform That Electrochemically Detects Anticancer Effects of Curcumin in a Multicellular Brain Cancer Model.

In this study, a multifunctional platform that enables the highly efficient formation of 3D multicellular cancer spheroids and precise real-time assessments of the anticancer effects of curcumin in a brain tumor coculture model is reported. A highly conductive gold nanostructure (HCGN) is fabricated to facilitate cancer spheroid formation without using anti-cell adhesion molecules. A neuroblastoma (SH-SY5Y) and glioblastoma (U-87MG) coculture model is generated on HCGN with a specific cell-to-cell ratio (SH-SY5Y: U-87MG = 1:1), and their redox behaviors are successfully measured without destroying the distinct 3D structure of the multicellular spheroids.

Vertically Coated Graphene Oxide Micro-Well Arrays for Highly Efficient Cancer Spheroid Formation and Drug Screening.

Research on the 3D culturing of cancer cells that better mimic in vivo solid tumors is important for efficient drug screening. Herein, a new platform that effectively facilitates the formation of cancer spheroids for anticancer drug screening is reported. Cytophilic graphene oxide (GO), when selectively coated on the sidewalls of micro-wells fabricated from a cell-adhesion-resistive polymer, is found to efficiently initiates distinct donut-like formation of cancer cell spheroids.

Enhancing Neurogenesis of Neural Stem Cells Using Homogeneous Nanohole Pattern-Modified Conductive Platform.

Biocompatible platforms, wherein cells attach and grow, are important for controlling cytoskeletal dynamics and steering stem cell functions, including differentiation. Among various components, membrane integrins play a key role in focal adhesion of cells (18-20 nm in size) and are, thus, highly sensitive to the nanotopographical features of underlying substrates. Hence, it is necessary to develop a platform/technique that can provide high flexibility in controlling nanostructure sizes.

A fibronectin-coated gold nanostructure composite for electrochemical detection of effects of curcumin-carrying nanoliposomes on human stomach cancer cells.

Curcumin, which is produced by the medicinal herbaceous plant Curcuma longa, has been widely investigated for use as a potential anticancer drug. In this study, the potential toxicity of curcumin-carrying nanoliposomes (curcumin-NLC) toward human stomach cancer cells (MKN-28) was investigated using a new cell-based electrochemical sensing platform. To satisfy both biocompatibility and electroconductivity of the electrodes, the density of the gold nanostructure and the coating conditions of extracellular matrix proteins (fibronectin and collagen) were optimized.

High density gold nanostructure composites for precise electrochemical detection of human embryonic stem cells in cell mixture.

Precise detection of undifferentiated human pluripotent stem cells (hPSCs) and their entire subsequent elimination are incredibly important in preventing teratoma formations after transplantation. Recently, electrochemical sensing platforms have demonstrated immense potential as a new tool to detect remaining hPSCs in label-free and non-destructive manner. Nevertheless, one of the critical huddles of this electrochemical sensing approach is its low sensitivity since even low concentrations of remaining hPSCs were reported to form teratoma once transplanted.

Nanobiosensing Platforms for Real-Time and Non-Invasive Monitoring of Stem Cell Pluripotency and Differentiation.

Breakthroughs in the biomedical and regenerative therapy fields have led to the influential ability of stem cells to differentiate into specific types of cells that enable the replacement of injured tissues/organs in the human body. Non-destructive identification of stem cell differentiation is highly necessary to avoid losses of differentiated cells, because most of the techniques generally used as confirmation tools for the successful differentiation of stem cells can result in valuable cells becoming irrecoverable. Regarding this issue, recent studies reported that both Raman spectroscopy and electrochemical sensing possess excellent characteristics for monitoring the behavior of stem cells, including differentiation.

Two-dimensional material-based bionano platforms to control mesenchymal stem cell differentiation.

Background: In the past decade, stem cells, with their ability to differentiate into various types of cells, have been proven to be resourceful in regenerative medicine and tissue engineering. Despite the ability to repair damaged parts of organs and tissues, the use of stem cells still entails several limitations, such as low differentiation efficiency and difficulties in guiding differentiation. To address these limitations, nanotechnology approaches have been recently implemented in stem cell research.

In situ label-free monitoring of human adipose-derived mesenchymal stem cell differentiation into multiple lineages.

Precise characterizations of stem cell differentiation into specific lineages, especially in non-destructive and non-invasive manner, are extremely important for generating patient-specific cells without mass loss of differentiated cells. Here, we report a new method capable of in situ label-free quantification of stem cell differentiation into multiple lineages, even at a single cell level. The human adipose-derived mesenchymal stem cells (hADMSCs) were first differentiated into two different types of cells (osteoblasts and adipocytes) and these differentiated cells were then intensively analyzed by micro-Raman spectroscopy.

Effects of two-dimensional materials on human mesenchymal stem cell behaviors.

Graphene, a typical two-dimensional (2D) material, is known to affect a variety of stem cell behaviors including adhesion, spreading, growth, and differentiation. Here, we report for the first time the effects of four different emerging 2D materials on human adipose-derived mesenchymal stem cells (hADMSCs). Graphene oxide (GO), molybdenum sulfide (MoS), tungsten sulfide (WS), and boron nitride (BN) were selected as model two-dimensional materials and were coated on cell-culture substrates by a drop-casting method.

Guiding osteogenesis of mesenchymal stem cells using carbon-based nanomaterials.

In the field of regenerative medicine, stem cells are highly promising due to their innate ability to generate multiple types of cells that could replace/repair damaged parts of human organs and tissues. It has been reported that both in vitro and in vivo function/survival of stem cells could significantly be improved by utilizing functional materials such as biodegradable polymers, metal composites, nanopatterns and nanohybrid particles. Of various biocompatible materials available for use in stem cell-based therapy and research, carbon-based materials-including fullerenes graphene/graphene oxide and carbon nanotubes-have been found to possess unique physicochemical characteristics that contribute to the effective guidance of stem cell differentiation into specific lineages.