scholarly journals Cartilage Tissue-Mimetic Pellets with Multifunctional Magnetic Hyaluronic Acid-Graft-Amphiphilic Gelatin Microcapsules for Chondrogenic Stimulation

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 785
Author(s):  
Kai-Ting Hou ◽  
Ting-Yu Liu ◽  
Min-Yu Chiang ◽  
Chun-Yu Chen ◽  
Shwu-Jen Chang ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Magnetic Stimulation ◽  
Early Stage ◽  
Superparamagnetic Iron Oxide ◽  
Cartilage Tissue ◽  
Specific Gene ◽  
High Cell ◽  
Gene Expressions ◽  
Articular Cartilage Defect ◽  
Specific Targeting

Articular cartilage defect is a common disorder caused by sustained mechanical stress. Owing to its nature of avascular, cartilage had less reconstruction ability so there is always a need for other repair strategies. In this study, we proposed tissue-mimetic pellets composed of chondrocytes and hyaluronic acid-graft-amphiphilic gelatin microcapsules (HA-AGMCs) to serve as biomimetic chondrocyte extracellular matrix (ECM) environments. The multifunctional HA-AGMC with specific targeting on CD44 receptors provides excellent structural stability and demonstrates high cell viability even in the center of pellets after 14 days culture. Furthermore, with superparamagnetic iron oxide nanoparticles (SPIOs) in the microcapsule shell of HA-AGMCs, it not only showed sound cell guiding ability but also induced two physical stimulations of static magnetic field(S) and magnet-derived shear stress (MF) on chondrogenic regeneration. Cartilage tissue-specific gene expressions of Col II and SOX9 were upregulated in the present of HA-AGMC in the early stage, and HA-AGMC+MF+S held the highest chondrogenic commitments throughout the study. Additionally, cartilage tissue-mimetic pellets with magnetic stimulation can stimulate chondrogenesis and sGAG synthesis.

scholarly journals Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 989
Author(s):  
Dhanashri Ingale ◽  
Priya Kulkarni ◽  
Ali Electricwala ◽  
Alpana Moghe ◽  
Sara Kamyab ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Early Stage ◽  
Challenge Test ◽  
Degradation Process ◽  
Cartilage Degradation ◽  
Gene Expressions ◽  
Inflammatory Microenvironment ◽  
Protein Levels ◽  
Advanced Stages ◽  
Inflammatory Milieu

Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1β, IL-15, PGE2 and NGF in early OA (Kellgren–Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1β and MMPs revealed expressional negative correlation.

scholarly journals Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie Shinohara ◽  
Hiroshi Arakawa ◽  
Yuuichi Oda ◽  
Nobuaki Shiraki ◽  
Shinji Sugiura ◽  
...  
Keyword(s):  
Normal Cell ◽  
Human Hepatocytes ◽  
New Drugs ◽  
Intestinal Cells ◽  
Specific Gene ◽  
Gene Expressions ◽  
Normal Cells ◽  
Pneumatic Pressure ◽  
Pressure Driven

AbstractExamining intestine–liver interactions is important for achieving the desired physiological drug absorption and metabolism response in in vitro drug tests. Multi-organ microphysiological systems (MPSs) constitute promising tools for evaluating inter-organ interactions in vitro. For coculture on MPSs, normal cells are challenging to use because they require complex maintenance and careful handling. Herein, we demonstrated the potential of coculturing normal cells on MPSs in the evaluation of intestine–liver interactions. To this end, we cocultured human-induced pluripotent stem cell-derived intestinal cells and fresh human hepatocytes which were isolated from PXB mice with medium circulation in a pneumatic-pressure-driven MPS with pipette-friendly liquid-handling options. The cytochrome activity, albumin production, and liver-specific gene expressions in human hepatocytes freshly isolated from a PXB mouse were significantly upregulated via coculture with hiPS-intestinal cells. Our normal cell coculture shows the effects of the interactions between the intestine and liver that may occur in vivo. This study is the first to demonstrate the coculturing of hiPS-intestinal cells and fresh human hepatocytes on an MPS for examining pure inter-organ interactions. Normal-cell coculture using the multi-organ MPS could be pursued to explore unknown physiological mechanisms of inter-organ interactions in vitro and investigate the physiological response of new drugs.

scholarly journals Digital Light Processing Bioprinted Human Chondrocyte-Laden Poly (γ-Glutamic Acid)/Hyaluronic Acid Bio-Ink towards Cartilage Tissue Engineering

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 714
Author(s):  
Alvin Kai-Xing Lee ◽  
Yen-Hong Lin ◽  
Chun-Hao Tsai ◽  
Wan-Ting Chang ◽  
Tsung-Li Lin ◽  
...  
Keyword(s):  
United States ◽  
Tissue Engineering ◽  
Hyaluronic Acid ◽  
Glutamic Acid ◽  
Cellular Proliferation ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
The United States ◽  
Cartilage Injury ◽  
Cartilage Tissue

Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.

scholarly journals Astrocytic transporters in Alzheimer's disease

2017 ◽  
Vol 474 (3) ◽  
pp. 333-355 ◽  
Author(s):  
Chris Ugbode ◽  
Yuhan Hu ◽  
Benjamin Whalley ◽  
Chris Peers ◽  
Marcus Rattray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Neurological Diseases ◽  
Current Evidence ◽  
Specific Targeting ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

pha-4 is Ce-fkh-1, a fork head/HNF-3alpha, beta, gamma homolog that functions in organogenesis of the C. elegans pharynx

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2171-2180 ◽  
Author(s):  
J.M. Kalb ◽  
K.K. Lau ◽  
B. Goszczynski ◽  
T. Fukushige ◽  
D. Moons ◽  
...  
Keyword(s):  
Early Stage ◽  
Sequence Similarity ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Specific Gene ◽  
Gata Factor ◽  
Enhancer Element ◽  
C Elegans ◽  
Fork Head ◽  
Organ Identity

The C. elegans Ce-fkh-1 gene has been cloned on the basis of its sequence similarity to the winged-helix DNA binding domain of the Drosophila fork head and mammalian HNF-3alpha, beta, gamma genes, and mutations in the zygotically active pha-4 gene have been shown to block formation of the pharynx (and rectum) at an early stage in embryogenesis. In the present paper, we show that Ce-fkh-1 and pha-4 are the same gene. We show that PHA-4 protein is present in nuclei of essentially all pharyngeal cells, of all five cell types. PHA-4 protein first appears close to the point at which a cell lineage will produce only pharyngeal cells, independently of cell type. We show that PHA-4 binds directly to a ‘pan-pharyngeal enhancer element’ previously identified in the promoter of the pharyngeal myosin myo-2 gene; in transgenic embryos, ectopic PHA-4 activates ectopic myo-2 expression. We also show that ectopic PHA-4 can activate ectopic expression of the ceh-22 gene, a pharyngeal-specific NK-2-type homeodomain protein previously shown to bind a muscle-specific enhancer near the PHA-4 binding site in the myo-2 promoter. We propose that it is the combination of pha-4 and regulatory molecules such as ceh-22 that produces the specific gene expression patterns during pharynx development. Overall, pha-4 can be described as an ‘organ identity factor’, completely necessary for organ formation, present in all cells of the organ from the earliest stages, capable of integrating upstream developmental pathways (in this case, the two distinct pathways that produce the anterior and posterior pharynx) and participating directly in the transcriptional regulation of organ specific genes. Finally, we note that the distribution of PHA-4 protein in C. elegans embryos is remarkably similar to the distribution of the fork head protein in Drosophila embryos: high levels in the foregut/pharynx and hindgut/rectum; low levels in the gut proper. Moreover, we show that pha-4 expression in the C. elegans gut is regulated by elt-2, a C. elegans gut-specific GATA-factor and possible homolog of the Drosophila gene serpent, which influences fork head expression in the fly gut. Overall, our results provide evidence for a highly conserved pathway regulating formation of the digestive tract in all (triploblastic) metazoa.

scholarly journals Dysregulation of MS risk genes and pathways at distinct stages of disease

2017 ◽  
Vol 4 (3) ◽  
pp. e337 ◽  
Author(s):  
Sundararajan Srinivasan ◽  
Marco Di Dario ◽  
Alessandra Russo ◽  
Ramesh Menon ◽  
Elena Brini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Gene List ◽  
Literature Mining ◽  
Specific Gene ◽  
Healthy Population ◽  
Gene Expressions ◽  
Altered Expression ◽  
Risk Genes

Objective:To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.Methods:We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.Results:Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage–specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.Conclusions:Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.

scholarly journals Correction: An injectable hyaluronic acid/PEG hydrogel for cartilage tissue engineering formed by integrating enzymatic crosslinking and Diels–Alder “click chemistry”

2018 ◽  
Vol 9 (28) ◽  
pp. 3959-3960 ◽  
Author(s):  
Feng Yu ◽  
Xiaodong Cao ◽  
Yuli Li ◽  
Lei Zeng ◽  
Bo Yuan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Hyaluronic Acid ◽  
Click Chemistry ◽  
Cartilage Tissue Engineering ◽  
Diels Alder ◽  
Cartilage Tissue

Correction for ‘An injectable hyaluronic acid/PEG hydrogel for cartilage tissue engineering formed by integrating enzymatic crosslinking and Diels–Alder “click chemistry”’ by Feng Yu et al., Polym. Chem., 2014, 5, 1082–1090.

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