Stem cell-based therapy for human diseases Hoang, Duc M.; Pham, Phuong T.; Bach, Trung Q. ...
Signal transduction and targeted therapy,
08/2022, Letnik:
7, Številka:
1
Journal Article
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Abstract
Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human ...pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.
In this paper, we describe the first data release of the Visible and Infrared Survey Telescope for Astronomy (VISTA) Deep Extragalactic Observations (VIDEO) survey. VIDEO is a ∼12 deg2 survey in the ...near-infrared Z, Y, J, H and K
s bands, specifically designed to enable the evolution of galaxies and large structures to be traced as a function of both epoch and environment from the present day out to z = 4, and active galactic nuclei (AGNs) and the most massive galaxies up to and into the epoch of reionization. With its depth and area, VIDEO will be able to fully explore the period in the Universe where AGN and starburst activity were at their peak and the first galaxy clusters were beginning to virialize. VIDEO therefore offers a unique data set with which to investigate the interplay between AGN, starbursts and environment, and the role of feedback at a time when it was potentially most crucial.
We provide data over the VIDEO-XMM3 tile, which also covers the Canada-France-Hawaii Telescope Legacy Survey Deep-1 field (CFHTLS-D1). The released VIDEO data reach a 5σ AB-magnitude depth of Z = 25.7, Y = 24.5, J = 24.4, H = 24.1 and K
s = 23.8 in 2 arcsec diameter apertures (the full depth of Y = 24.6 will be reached within the full integration time in future releases). The data are compared to previous surveys over this field and we find good astrometric agreement with the Two Micron All Sky Survey, and source counts in agreement with the recently released UltraVISTA survey data. The addition of the VIDEO data to the CFHTLS-D1 optical data increases the accuracy of photometric redshifts and significantly reduces the fraction of catastrophic outliers over the redshift range 0 < z < 1 from 5.8 to 3.1 per cent in the absence of an i-band luminosity prior. However, we expect that the main improvement in photometric redshifts will come in the redshift range 1 < z < 4 due to the sensitivity to the Balmer and 4000 Å breaks provided by the near-infrared VISTA filters. All images and catalogues presented in this paper are publicly available through ESO's phase 3 archive and the VISTA Science Archive.
Background
The relationship between dental anxiety and mucosal wound healing, especially the inflammatory response, has not been well studied. This study aimed to examine the relationship between ...anxiety prior to dental treatment and short‐term inflammation following impacted mandibular third molar (IMTM) surgery.
Methods
Fifty‐nine patients who required IMTM surgery were recruited for this study. Sample demographics (gender, age) and surgical extent (Pederson classification, duration) were collected. Psychological stress towards surgery was assessed by the Dental Fear Survey (DFS). All surgeries were conducted according to an identical surgical protocol and all patients were given the same medical prescription. Correlations between short‐term inflammation (swelling and trismus after 2 days) and DFS, demographics and surgical extent were statistically analysed.
Results
The results showed that patients with a higher DFS score demonstrated more severe swelling (β = 0.36, P = 0.016) and trismus (β = 0.37, P = 0.008) 2 days after surgery. In addition, more severe trismus occurred following more difficult surgery (β = 0.29, P = 0.016) or that with a longer duration (β = 0.21, P = 0.081). Neither gender nor age showed any significant relationship with swelling or trismus.
Conclusion
Short‐term inflammatory response following IMTM surgery correlated with the preoperative dental anxiety and this correlation was independent of gender and surgical extent.
We use the BISICLES adaptive mesh ice sheet model to carry out one, two, and three century simulations of the fast-flowing ice streams of the West Antarctic Ice Sheet, deploying sub-kilometer ...resolution around the grounding line since coarser resolution results in substantial underestimation of the response. Each of the simulations begins with a geometry and velocity close to present-day observations, and evolves according to variation in meteoric ice accumulation rates and oceanic ice shelf melt rates. Future changes in accumulation and melt rates range from no change, through anomalies computed by atmosphere and ocean models driven by the E1 and A1B emissions scenarios, to spatially uniform melt rate anomalies that remove most of the ice shelves over a few centuries. We find that variation in the resulting ice dynamics is dominated by the choice of initial conditions and ice shelf melt rate and mesh resolution, although ice accumulation affects the net change in volume above flotation to a similar degree. Given sufficient melt rates, we compute grounding line retreat over hundreds of kilometers in every major ice stream, but the ocean models do not predict such melt rates outside of the Amundsen Sea Embayment until after 2100. Within the Amundsen Sea Embayment the largest single source of variability is the onset of sustained retreat in Thwaites Glacier, which can triple the rate of eustatic sea level rise.
Childhood obesity is a complex issue and needs multistakeholder involvement at all levels to foster healthier lifestyles in a sustainable way. ‘Ensemble Prévenons l'ObésitéDes Enfants’ (EPODE, ...Together Let's Prevent Childhood Obesity) is a large‐scale, coordinated, capacity‐building approach for communities to implement effective and sustainable strategies to prevent childhood obesity. This paper describes EPODE methodology and its objective of preventing childhood obesity. At a central level, a coordination team, using social marketing and organizational techniques, trains and coaches a local project manager nominated in each EPODE community by the local authorities. The local project manager is also provided with tools to mobilize local stakeholders through a local steering committee and local networks. The added value of the methodology is to mobilize stakeholders at all levels across the public and the private sectors. Its critical components include political commitment, sustainable resources, support services and a strong scientific input – drawing on the evidence‐base – together with evaluation of the programme. Since 2004, EPODE methodology has been implemented in more than 500 communities in six countries. Community‐based interventions are integral to childhood obesity prevention. EPODE provides a valuable model to address this challenge.
Regulatory T (Treg) cells maintain immune tolerance through the master transcription factor forkhead box P3 (FOXP3), which is crucial for Treg cell function and homeostasis. We identified an IPEX ...(immune dysregulation polyendocrinopathy enteropathy X-linked) syndrome patient with a FOXP3 mutation in the domain swap interface of the protein. Recapitulation of this Foxp3 variant in mice led to the development of an autoimmune syndrome consistent with an unrestrained T helper type 2 (Th2) immune response. Genomic analysis of Treg cells by RNA-sequencing, Foxp3 chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-sequencing), and H3K27ac-HiChIP revealed a specific de-repression of the Th2 transcriptional program leading to the generation of Th2-like Treg cells that were unable to suppress extrinsic Th2 cells. Th2-like Treg cells showed increased intra-chromosomal interactions in the Th2 locus, leading to type 2 cytokine production. These findings identify a direct role for Foxp3 in suppressing Th2-like Treg cells and implicate additional pathways that could be targeted to restrain Th2 trans-differentiated Treg cells.
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•IPEX mutation M370I leads to unrestrained Th2 immune response•M370I mutation generates Th2-like Treg cells expressing GATA3 and Th2 cytokines•M370I mutation induces de novo Foxp3 binding sites in the Th2 locus•M370I Treg cells have increased chromatin interaction at the Th2 locus
Naturally occurring FOXP3 mutations provide unique opportunities to leverage clinical observations to increase our understanding of fundamental Treg cell biology. Van Gool et al. identify a mutation in the domain-swap interface of FOXP3 in IPEX patients and demonstrate a direct role for the mutant FOXP3 in reprogramming Treg cells to acquire a Th2-like phenotype, leading to Th2-mediated autoimmunity.
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