Secretome of the Olfactory Ensheathing Cells Influences the Behavior of Neural Stem Cells.

Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear.

Improving iPSC Differentiation Using a Nanodot Platform.

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation.

Therapeutic effect of induced pluripotent stem cell -derived extracellular vesicles in an and osteoarthritis model.

Background/objective: Osteoarthritis (OA) is a multifactorial joint disease associated with the deterioration of chondrocytes and inflammation. Treatment of OA is only aimed at reducing pain and improving joint function. Recently, extracellular vesicles (EVs) secreted from stem cells have emerged as a cell regenerative tool in several degenerative diseases, including OA.

Electrically Copolymerized Polydopamine Melanin/Poly(3,4-ethylenedioxythiophene) Applied for Bioactive Multimodal Neural Interfaces with Induced Pluripotent Stem Cell-Derived Neurons.

Multimodal neural interfaces include combined functions of electrical neuromodulation and synchronic monitoring of neurochemical and physiological signals in one device. The remarkable biocompatibility and electrochemical performance of polystyrene sulfonate-doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) have made it the most recommended conductive polymer neural electrode material. However, PEDOT:PSS formed by electrochemical deposition, called PEDOT/PSS, often need multiple doping to improve structural instability in moisture, resolve the difficulties of functionalization, and overcome the poor cellular affinity.

Development of a combination antibiogram for empirical treatments of Pseudomonas aeruginosa at a university-affiliated teaching hospital.

Introduction: The significantly higher mortality rate in the critical illness patients with Pseudomonas aeruginosa (PA) infection is linked to inappropriate selecting of empirical treatment. Traditional local antibiogram provides clinicians the resistant rate of a single antimicrobial agent to the pathogen in the specific setting. The information is valuable to the clinicians in selecting suitable empirical antibiotic therapy.

High-Density Horizontal Stacking of Chondrocytes via the Synergy of Biocompatible Magnetic Gelatin Nanocarriers and Internal Magnetic Navigation for Enhancing Cartilage Repair.

Osteoarthritis (OA) is a globally occurring articular cartilage degeneration disease that adversely affects both the physical and mental well-being of the patient, including limited mobility. One major pathological characteristic of OA is primarily related to articular cartilage defects resulting from abrasion and catabolic and proinflammatory mediators in OA joints. Although cell therapy has hitherto been regarded as a promising treatment for OA, the therapeutic effects did not meet expectations due to the outflow of implanted cells.

Anti-Excitotoxic Effects of N-Butylidenephthalide Revealed by Chemically Insulted Purkinje Progenitor Cells Derived from SCA3 iPSCs.

Spinocerebellar ataxia type 3 (SCA3) is characterized by the over-repetitive CAG codon in the ataxin-3 gene (), which encodes the mutant ATXN3 protein. The pathological defects of SCA3 such as the impaired aggresomes, autophagy, and the proteasome have been reported previously. To date, no effective treatment is available for SCA3 disease.

Tissue-level alveolar epithelium model for recapitulating SARS-CoV-2 infection and cellular plasticity.

Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; however, suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. In this paper, we present a standardized primary alveolar cell culture method for establishing a human alveolar epithelium model that can recapitulate viral infection and cellular plasticity. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry into the alveolar type-I/II cells, cytokine production activation, and pulmonary surfactant destruction are reproduced.

A smart injectable composite hydrogel with magnetic navigation and controlled glutathione release for promoting chondrocyte array and self-healing in damaged cartilage tissue.

Injectable cell-based hydrogels allow surgical operation in a minimally invasive way for articular cartilage lesions but the chondrocytes in the injectable hydrogels are difficultly arrayed and fixed at the site of interest to repair the cartilage tissue. In this study, an injectable hyaluronic acid-polyacrylic acid (HA-pAA) hydrogel was first synthesized using hyaluronic acid-cyclodextrin (HA-CD) and polyacrylic acid-ferrocene (pAA-Fc) to provide cell-delivery and self-healing. To promote the cell fixation and alignment, porous poly(lactic--glycolic acid) (PLGA) magnetic microcapsules (PPMMs) with glutathione (GSH) loaded and iron oxide nanoparticles (IO) located in the shell were designed.

Ansamitocin P3-Loaded Gold-NanoCage Conjugated with Immune Checkpoint Inhibitor to Enhance Photo-Chemo-Thermal Maturation of Dendritic Cells for Hepatocellular Carcinoma.

Immunotherapy is a newly developed method for cancer treatment, but still generates limited response in partial patients for hepatocellular carcinoma (HCC) because the immunity cycle is limited by the tumor microenvironment (TME). Herein, we introduce multifunctional gold nanocages (AuNCs)-based nanocarriers with Ansamitocin P3 (AP3) loaded and anti-PDL1 binding (AP3-AuNCs-anti-PDL1) which can combine photothermal therapy, chemotherapeutic agent-triggered DCs maturation, and checkpoint immunotherapy in one platform. The AP3-AuNCs-anti-PDL1 using Avidin-biotin to bind anti-PDL1 on the surface of AP3-AuNCs showed specifically cellular targeting compared to AuNCs, which can increase the immune responses.

Generation of IBMS-iPSC-015, -016, -017 human induced pluripotent stem cells (IBMSi013-A, IBMSi014-A, and IBMSi015-A) derived from patients with atrial fibrillation.

Atrial fibrillation is the most common heart disease in the world, with around 35 million patients in 2020. Here we reported the generation of IBMS-iPSC-015-06, IBMS-iPSC-016-06, and IBMS-iPSC-017-02 as human induced pluripotent stem cell (iPSC) lines from patients' peripheral blood mononuclear cells (PBMCs) with atrial fibrillation. The cell lines expressed properties of pluripotent stem cells, including pluripotent markers and the ability to differentiate into three germ layers.

Generation of IBMS-iPSC-021, -022, -023 human induced pluripotent stem cells (IBMSi016-A, IBMSi017-A, and IBMSi018-A) derived from patients with the ALDH2 rs671 polymorphism.

ALDH2 gene is coded for the aldehyde dehydrogenase (ALDH), which is an enzyme involved in alcohol metabolism. Compared to normal aldehyde dehydrogenases, a homozygous point mutation on exon 12 from G to A significantly reduces its efficiency. In this study, we have reported the generation of IBMS-iPSC-021-04, IBMS-iPSC-022-01, and IBMS-iPSC-023-03 as induced pluripotent stem cell (iPSC) lines carrying the homozygous form of ALDH2 with the rs671 genetic polymorphism (E487K mutation).

4D spatiotemporal modulation of biomolecules distribution in anisotropic corrugated microwrinkles via electrically manipulated microcapsules within hierarchical hydrogel for spinal cord regeneration.

Although traditional 3D scaffolds or biomimetic hydrogels have been used for tissue engineering and regenerative medicine, soft tissue microenvironment usually has a highly anisotropic structure and a dynamically controllable deformation with various biomolecule distribution. In this study, we developed a hierarchical hybrid gelatin methacrylate-microcapsule hydrogel (HGMH) with Neurotrophin-3(NT-3)-loaded PLGA microcapsules to fabricate anisotropic structure with patterned NT-3 distribution (demonstrated as striped and triangular patterns) by dielectrophoresis (DEP). The HGMH provides a dynamic biomimetic sinuate-microwrinkles change with NT-3 spatial gradient and 2-stage time-dependent distribution, which was further simulated using a 3D finite element model.

Generation of induced pluripotent stem cells FIRDIi001-A from a Taiwanese subject carrying ALDH2 pE487K mutation.

The ALDH2 mutation (ALDH2*2) is caused by an amino acid substitution ALDH2 rs671 G>A (pE487K) which reduces ALDH2 enzyme activity. When individuals with the ALDH2 mutation consume alcohol, accumulating acetaldehyde in the blood can cause reddened face, headache, nausea, and palpitations; symptoms referred to as Alcohol Flushing Reaction. We report the production of an induced pluripotent stem cell (iPSC) line, FIRDIi001-A, developed from peripheral blood mononuclear cells of a 39-year-old male subject with the ALDH2*2 mutation.

Copy number variant hotspots in Han Taiwanese population induced pluripotent stem cell lines - lessons from establishing the Taiwan human disease iPSC Consortium Bank.

Background: The Taiwan Human Disease iPSC Service Consortium was established to accelerate Taiwan's growing stem cell research initiatives and provide a platform for researchers interested in utilizing induced pluripotent stem cell (iPSC) technology. The consortium has generated and characterized 83 iPSC lines: 11 normal and 72 disease iPSC lines covering 21 different diseases, several of which are of high incidence in Taiwan. Whether there are any reprogramming-induced recurrent copy number variant (CNV) hotspots in iPSCs is still largely unknown.

Organ-on-a-Chip: Opportunities for Assessing the Toxicity of Particulate Matter.

Recent developments in epidemiology have confirmed that airborne particulates are directly associated with respiratory pathology and mortality. Although clinical studies have yielded evidence of the effects of many types of fine particulates on human health, it still does not have a complete understanding of how physiological reactions are caused nor to the changes and damages associated with cellular and molecular mechanisms. Currently, most health assessment studies of particulate matter (PM) are conducted through cell culture or animal experiments.

Generation of a gene corrected human isogenic IBMS-iPSC-014-C from polycystic-kidney-disease induced pluripotent stem cell line using CRISPR/Cas9.

We report the engendering an isogenic iPSC line from the IBMS-iPSC-014-05 with homozygous correction of the R803X, Chr4: 88989098C > T in PKD2, using CRISPR/Cas9 technology. The results from the isogenic control, IBMS-iPSC-014-05C, showed that mutation had been corrected, while maintaining normal morphology, pluripotency, and differentiation capacity into three germ layers.

Generation of a human induced pluripotent stem cell (iPSC) line (IBMS-iPSC-048-05) from a patient with ALS and parkinsonism having a hexanucleotide repeat expansion mutation in C9orf72 gene.

A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) gene causes a heterogeneous neurodegenerative disorder that includes amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and parkinsonism. Here, we used the Sendai virus delivery system to generate induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of a male patient with an increased hexanucleotide repeat expansion in C9orf72. The resulting iPSCs exhibited pluripotency, confirmed by immunofluorescent staining for pluripotency markers, and differentiated into three germ layers in vivo.

Generation of induced pluripotent stem cells MMCi001-A from a Taiwanese hearing loss patient carrying GJB2 pV37I mutation.

Hearing loss is the most common disorder in the sensory system. Mutations in GJB2 have been reported to be very common in sensorineural hearing loss patients. In this report, we generated an induced pluripotent stem cell (iPSC) line, MMCi001-A, from the peripheral blood mononuclear cells of a 4-year-old male hearing loss patient carrying GJB2 pV37I mutation by using the Sendai virus delivery system.

The Development of Controllable Magnetic Driven Microphysiological System.

Current research has enabled the use of microphysiological systems and creation of models for alveolar and pulmonary diseases. However, bottlenecks remain in terms of medium- and long-term regulation of cell cultures and their functions in microchannel systems, as well as in the enhancement of representation of alveolar models and reference values of the data. Currently used systems also require on-chip manufacturing of complex units, such as pumps, tubes, and other cumbersome structures for maintaining cells in culture.

Generation of induced pluripotent stem cells (IBMSi011-A) from a patient with Parkinson's disease carrying LRRK2 p.I1371V mutation.

Leucine rich repeat kinase 2 (LRRK2) is the causative gene for autosomal-dominant familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with LRRK2 c.4111A > G (p.

Generation of induced pluripotent stem cell line-NTUHi001-A from a premature ovarian failure patient with Turner's syndrome mosaicism.

Turner's syndrome (TS) is one of the main causes of premature ovarian failure (POF). However, the mechanisms underlying POF are difficult to study due to the lack of suitable disease models. Herein, we have generated a human induced pluripotent stem cell (hiPSC) line derived from the peripheral blood mononuclear cells of a female patient with Turner's syndrome mosaicism via integration-free Sendai-virus system.

Reprogramming of a human induced pluripotent stem cell (iPSC) line (IBMSi012-A) from an early-onset Parkinson's disease patient harboring a homozygous p.D331Y mutation in the PLA2G6 gene.

A recessive mutation in PLA2G6, which is known to cause a heterogeneous neurodegenerative clinical spectrum, has recently been shown to be responsible for autosomal-recessive familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with a homozygous PLA2G6 c.991G > T (p.

Generation of induced pluripotent stem cells from a patient with X-linked juvenile retinoschisis.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal dystrophy manifested as splitting of anatomical layers of retina. In this report, we generated a patient-specific induced pluripotent stem cell (iPSC) line, TVGH-iPSC-013-05, from the peripheral blood mononuclear cells of a male patient with XLRS by using the Sendai-virus delivery system. We believe that XLRS patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.