From organoids to organoids-on-a-chip: Current applications and challenges in biomedical research.

The high failure rates in clinical drug development based on animal models highlight the urgent need for more representative human models in biomedical research. In response to this demand, organoids and organ chips were integrated for greater physiological relevance and dynamic, controlled experimental conditions. This innovative platform-the organoids-on-a-chip technology-shows great promise in disease modeling, drug discovery, and personalized medicine, attracting interest from researchers, clinicians, regulatory authorities, and industry stakeholders.

Human Midbrain Organoids Enriched With Dopaminergic Neurons for Long-Term Functional Evaluation.

Human midbrain organoids with functional dopaminergic (DA) neurons are invaluable for the therapeutic development of Parkinson's disease (PD). However, current methods face significant limitations, including challenges in generating pint-sized organoids enriched with DA neurons and the lack of robust functional assays for efficiently evaluating neural networks over extended periods. Here we present an innovative approach that combines developmental patterning with mechanical cutting to produce small midbrain organoids, with diameters less than 300 μm, suitable for long-term evaluation, along with a comprehensive functional assay system consisting of calcium transient assay, neurite extension assay, and multielectrode array (MEA) assay.

CD4-Derived Double-Negative T Cells Ameliorate Alzheimer's Disease-Like Phenotypes in the 5×FAD Mouse Model.

Background: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder that is difficult to predict and is typically diagnosed only after symptoms manifest. Recently, CD4 T cell-derived double-negative T (DNT) cells have shown strong immuno-regulatory properties in both in vitro and in vivo neuronal inflammation studies. However, the effectiveness of DNT cells in treating on AD are not yet fully understood.

Research hotspots and trends of microRNAs in spinal cord injury: a comprehensive bibliometric analysis.

Background: Spinal cord injury (SCI) is a nervous system disease leading to motor and sensory dysfunction below the injury level, and can result in paralysis. MicroRNAs (miRNAs) play a key role in SCI treatment, and related research provides insights for SCI diagnosis and treatment. Bibliometrics is an important tool for literature statistics and evaluation, objectively summarizing multidimensional information.

Induction of local immunosuppression in allogeneic cell transplantation by cell-type-specific expression of PD-L1 and CTLA4Ig.

Immune rejection has long hindered allogeneic cell transplantation therapy. Current genetic modification approaches, including direct targeting of major histocompatibility complex or constitutive expression of immune inhibitory molecules, exhibit drawbacks such as severe adverse effects or elevated tumorigenesis risks. To overcome these limitations, we introduce an innovative approach to induce cell-type-specific immune tolerance in differentiated cells.

Safety and efficacy of human ESC-derived corneal endothelial cells for corneal endothelial dysfunction.

Background: Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge.

Human midbrain dopaminergic progenitors.

Human midbrain dopaminergic progenitors (mDAPs) are one of the most representative cell types in both basic research and clinical applications. However, there are still many challenges for the preparation and quality control of mDAPs, such as the lack of standards. Therefore, the establishment of critical quality attributes and technical specifications for mDAPs is largely needed.

Human neural stem cells.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022.

Technical specifications for ethics review of human stem cell research.

The rapid advancement of human stem cell research and its expansion into emerging areas has resulted in an escalation of ethical challenges associated with these studies. As a result, there has been a corresponding increase in both the volume and complexity of institutional ethics reviews, coupled with higher expectations for the quality of the review process. In response to these challenges, this standard provides a comprehensive outline of the fundamental principles, content, types, and procedures of ethics review, specifically focusing on non-clinical human stem cell research.

Abnormal chromatin remodeling caused by ARID1A deletion leads to malformation of the dentate gyrus.

ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be a tumor suppressor. Recently, loss-of-function of ARID1A gene has been shown to cause intellectual disability. Here we generate Arid1a conditional knockout mice and investigate Arid1a function in the hippocampus.

One-step cell biomanufacturing platform: porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation and survival after transplantation .

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson's disease. Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson's disease. However, transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.

An aggregation of human embryonic and trophoblast stem cells reveals the role of trophectoderm on epiblast differentiation.

The interactions between extra-embryonic tissues and embryonic tissues are crucial to ensure proper early embryo development. However, the understanding of the crosstalk between the embryonic tissues and extra-embryonic tissues is lacking, mainly due to ethical restrictions, difficulties in obtaining natural human embryos, and lack of appropriate in vitro models. Here by aggregating human embryonic stem cells (hESCs) with human trophoblast stem cells (hTSCs), we revealed the hESCs robustly self-organized into a unique asymmetric structure which the primitive streak (PS) like cells exclusively distributed at the distal end to the TS-compartment, and morphologically flattened cells, presumed to be the extra-embryonic mesoderm cells (EXMC) like cells, were induced at the proximal end to hTSCs.

Lipopolysaccharide Preconditioning Restricts Microglial Overactivation and Alleviates Inflammation-Induced Depressive-like Behavior in Mice.

Overactive microglia and severe neuroinflammation play crucial roles in the development of major depressive disorder. Preconditioning with lipopolysaccharide (LPS) provides protection against severe neuroinflammation. However, administering high doses of LPS to mice triggers depressive symptoms.

Endothelial Arid1a deletion disrupts the balance among angiogenesis, neurogenesis and gliogenesis in the developing brain.

The vascular system and the neural system processes occur simultaneously, the interaction among them is fundamental to the normal development of the central nervous system. Arid1a (AT-rich interaction domain 1A), which encodes an epigenetic subunit of the SWI/SNF chromatin-remodelling complex, is associated with promoter-mediated gene regulation and histone modification. However, the molecular mechanism of the interaction between cerebrovascular and neural progenitor cells (NPCs) remains unclear.

Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice.

Microglia are the primary source of transglutaminase 2 (TGM2) in the brain; however, the roles of microglial TGM2 in neural development and disease are still not well known. The aim of this study is to elucidate the role and mechanisms of microglial TGM2 in the brain. A mouse line with a specific knockout of Tgm2 in microglia was generated.

Generation of human otic neuronal organoids using pluripotent stem cells.

Otic neurons, also known as spiral ganglion neurons (SGNs) in mammalian cochlea, transmit electrical signals from sensory hair cells to cochlear nuclei of the auditory system. SGNs are sensitive to toxic insults, vulnerable to get irreversible damaged and hardly regenerate after damage, causing persistent sensorineural hearing loss. Yet, to get authentic SGNs for research or therapeutic purpose remains challenging.

A Human-Specific De Novo Gene Promotes Cortical Expansion and Folding.

Newly originated de novo genes have been linked to the formation and function of the human brain. However, how a specific gene originates from ancestral noncoding DNAs and becomes involved in the preexisting network for functional outcomes remains elusive. Here, a human-specific de novo gene, SP0535, is identified that is preferentially expressed in the ventricular zone of the human fetal brain and plays an important role in cortical development and function.

De novo genes with an lncRNA origin encode unique human brain developmental functionality.

Human de novo genes can originate from neutral long non-coding RNA (lncRNA) loci and are evolutionarily significant in general, yet how and why this all-or-nothing transition to functionality happens remains unclear. Here, in 74 human/hominoid-specific de novo genes, we identified distinctive U1 elements and RNA splice-related sequences accounting for RNA nuclear export, differentiating mRNAs from lncRNAs, and driving the origin of de novo genes from lncRNA loci. The polymorphic sites facilitating the lncRNA-mRNA conversion through regulating nuclear export are selectively constrained, maintaining a boundary that differentiates mRNAs from lncRNAs.

Single-cell transcriptomics reveals the cell fate transitions of human dopaminergic progenitors derived from hESCs.

Background: Midbrain dopaminergic (DA) progenitors derived from human pluripotent stem cells are considered to be a promising treatment for Parkinson's disease (PD). However, the differentiation process produces undesired cell types, which influence the in vivo evaluation of DA cells. In this paper, we analyze the cell fate choice during differentiation and provide valuable information on cell preparation.