Abstract
Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for ...OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes controlling OA progression is poor. Here, we report the association of OA with increased levels of osteoclast-associated receptor (OSCAR), an immunoglobulin-like collagen-recognition receptor. In mice, OSCAR deletion abrogates OA manifestations, such as articular cartilage destruction, subchondral bone sclerosis, and hyaline cartilage loss. These effects are a result of decreased chondrocyte apoptosis, which is caused by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in induced OA. Treatments with human OSCAR-Fc fusion protein attenuates OA pathogenesis caused by experimental OA. Thus, this work highlights the function of OSCAR as a catabolic regulator of OA pathogenesis, indicating that OSCAR blockade is a potential therapy for OA.
Embryonic stem cells hold great promise for various diseases because of their unlimited capacity for self-renewal and ability to differentiate into any cell type in the body. However, despite over 3 ...decades of research, there have been no reports on the safety and potential efficacy of pluripotent stem cell progeny in Asian patients with any disease. Here, we report the safety and tolerability of subretinal transplantation of human embryonic-stem-cell (hESC)-derived retinal pigment epithelium in four Asian patients: two with dry age-related macular degeneration and two with Stargardt macular dystrophy. They were followed for 1 year. There was no evidence of adverse proliferation, tumorigenicity, ectopic tissue formation, or other serious safety issues related to the transplanted cells. Visual acuity improved 9–19 letters in three patients and remained stable (+1 letter) in one patient. The results confirmed that hESC-derived cells could serve as a potentially safe new source for regenerative medicine.
•Human embryonic-stem-cell-derived retinal pigment epithelial cells were transplanted•Patches of increasing pigmentations were observed after transplantation of the cells•Visual function stabilized or improved in all of these macular degeneration patients•There were no serious adverse events associated with the cells up to 1 year
In this article, Lanza, Song, and colleagues show the feasibility and preliminary safety of human embryonic-stem-cell-derived retinal pigment epithelial cell therapy. Visual acuity stabilized or improved in all of the patients. Continued follow-up and further study are needed to determine the long-term safety and efficacy.
Derivation of patient-specific human pluripotent stem cells via somatic cell nuclear transfer (SCNT) has the potential for applications in a range of therapeutic contexts. However, successful SCNT ...with human cells has proved challenging to achieve, and thus far has only been reported with fetal or infant somatic cells. In this study, we describe the application of a recently developed methodology for the generation of human ESCs via SCNT using dermal fibroblasts from 35- and 75-year-old males. Our study therefore demonstrates the applicability of SCNT for adult human cells and supports further investigation of SCNT as a strategy for regenerative medicine.
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•Adult cell reprogramming via SCNT is not successful via the conventional protocol•Improved success was achieved with a recently developed approach•hESCs were derived via SCNT from 35- and 75-year-old males
Chung et al. show that recently developed technology that enables human SCNT reprogramming from embryonic cells is also effective with donor cells from adults, enhancing the therapeutic potential of this approach.
To evaluate not only the risk of total preterm birth (PTB) but also spontaneous preterm birth (sPTB) and indicated preterm birth (iPTB) in vanishing twin (VT).
This is a secondary analysis of a ...multicenter prospective cohort study. In 12 different healthcare institutions, women with singleton pregnancies were enrolled in early pregnancy and followed up till delivery.
A total of 4,746 women were included in the final analysis, and. the frequency of VT was 1.1% (54/4746). VT group had a higher risk for total PTB (PTB<34 weeks, 2.1% vs. 14.8%, p<0.001; PTB<32 weeks, 1.6% vs. 13.0%, p<0.001; PTB<28 weeks, 0.9% vs. 13.0%, p<0.001) than singleton group. The VT group had increased risk for both sPTB and iPTB (<34 weeks, <32 weeks, and <28 weeks), and this increased risk for sPTB and iPTB in VT group remained significant even after controlling for confounders such as maternal age, parity, pre-pregnancy BMI, and mode of conception.
Vanishing twin can be an independent risk factor for both sPTB and iPTB when compared with singleton pregnancy.
Defect less semiconductor-on-insulator (-OI) by a cost-effective and low-temperature process is strongly needed for monolithic 3-D integration. Toward this, in this paper, we present a cost-effective ...fabrication of the indium gallium arsenide-OI structure featuring the direct wafer bonding (DWB) and epitaxial lift-off (ELO) techniques as well as the reuse of the indium phosphide donor wafer. We systematically investigated the effects of the prepatterning of the III-V layer before DWB and surface reforming (hydrophilic) to speed up the ELO process for a fast and high-throughput process, which is essential for cost reduction. This method provides an excellent crystal quality of In 0.53 Ga 0.47 As on Si. Crystal quality of the film was evaluated using Raman spectra, and transmission electron microscope. Finally, we achieved good electrical properties of In 0.53 Ga 0.47 As-OI metal-oxide-semiconductor field-effect-transistors fabricated through the proposed DWB and ELO.
To evaluate adverse obstetric outcomes in women with a history of endometrial cancer (EC).
Population-based cohort study.
The Korean National Health Insurance (KNHI) claims database.
Women who gave ...birth between 2009 and 2016, with a history of EC prior to pregnancy.
The KNHI database was used to compare obstetric outcomes of women with and without a history of EC, using the ICD-10 codes. Multivariable logistic regression models were used to determine the associations between a history of EC and adverse obstetric outcomes.
Adverse obstetric outcomes.
Overall, 248 and 3 335 359 women with and without a history of EC, respectively, gave birth. When adjusted for age, primiparity and comorbidities, an increased risk of multiple gestations (odds ratio OR 4.925, 95% confidence interval CI 3.394-7.147), caesarean delivery (OR 2.005, 95% CI 1.535-2.62) and preterm birth (OR 1.941, 95% CI 1.107-3.404) was observed among women with a history of EC. We were unable to demonstrate significant differences in the risk of pre-eclampsia, gestational diabetes, vacuum delivery, placenta praevia, placenta accreta spectrum, placental abruption and postpartum haemorrhage between the groups. In the sensitivity analyses excluding multiple gestations, an increased risk of preterm birth was not observed among women with a history of EC (OR 1.276, 95% CI 0.565-2.881).
There is no convincing evidence of an increased risk of adverse obstetric outcomes among women with a history of EC. Our findings would be useful in counselling of patients with EC who are undergoing fertility-sparing treatment.
The future of safe cell-based therapy rests on overcoming teratoma/tumor formation, in particular when using human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human ...induced pluripotent stem cells (hiPSCs). Because the presence of a few remaining undifferentiated hPSCs can cause undesirable teratomas after transplantation, complete removal of these cells with no/minimal damage to differentiated cells is a prerequisite for clinical application of hPSC-based therapy. Having identified a unique hESC signature of pro- and antiapoptotic gene expression profile, we hypothesized that targeting hPSC-specific antiapoptotic factor(s) (i.e., survivin or Bcl10) represents an efficient strategy to selectively eliminate pluripotent cells with teratoma potential. Here we report the successful identification of small molecules that can effectively inhibit these antiapoptotic factors, leading to selective and efficient removal of pluripotent stem cells through apoptotic cell death. In particular, a single treatment of hESC-derived mixed population with chemical inhibitors of survivin (e.g., quercetin or YM155) induced selective and complete cell death of undifferentiated hPSCs. In contrast, differentiated cell types (e.g., dopamine neurons and smooth-muscle cells) derived from hPSCs survived well and maintained their functionality. We found that quercetin-induced selective cell death is caused by mitochondrial accumulation of p53 and is sufficient to prevent teratoma formation after transplantation of hESC- or hiPSC-derived cells. Taken together, these results provide the “proof of concept” that small-molecule targeting of hPSC-specific antiapoptotic pathway(s) is a viable strategy to prevent tumor formation by selectively eliminating remaining undifferentiated pluripotent cells for safe hPSC-based therapy.
Non-invasive prenatal screening (NIPS) of trisomy 21 (T21) using digital PCR (dPCR) with several advantages will be very effective. Here, we developed a dPCR system for T21 screening which allows ...high sensitivity and real-time diagnosis and thus overcome sequence based analysis.
Cut-off value was established using DNA extracted from all 157 T21 negative samples including 47 pregnant woman samples and 3 T21 positive pregnant woman samples extracted from 4 different sample types. To increase the portion of the cell-free fetal DNA (cffDNA) in maternal cell-free DNA (cfDNA), a size selection method was devised. We evaluated the clinical reliability of NIPS using dPCR through analysis of 877 pregnant woman samples.
We could demonstrate the possibility of NIPS using dPCR performed by applying cut-off value and size selection method. The overall accuracy was derived at 99.66% using 877 pregnant woman plasma samples.
Our results showed that dPCR can meet the requirements for NIPS for T21. It is relatively inexpensive, easy to use in a screening method and compatible with ethical concerns regarding access to nucleotide sequence information. This study may be a basic data for the development of population-wide screening for T21 in pregnant women.
•NIPS for trisomy 21 using dPCR is easy to apply and results are obtained quickly•We have developed the technology using digital PCR to screening for trisomy 21•We evaluated the accuracy of development technology using clinical samples•This technique can be extended to the detection of other aneuploidies using cfDNA
A few studies have mentioned that post-bronchoscopy sputum (PBS) could improve the diagnostic yield in pauci-bacillary pulmonary tuberculosis (PTB). Therefore, we evaluated the diagnostic yield of ...PBS for diagnosing pauci-bacillaryPTB.
Clinical data of immunocompromised adult patients with pauci-bacillary PTB were retrospectively retrieved at a tertiary hospital in Seoul, South Korea over a 5-year period. We analyzed patients who underwent bronchoscopy examinations for diagnosing pauci-bacillary PTB.
Ninety patients were finally analyzed. Of these patients, 76 patients were tested with PBS. Six (8%) of these patients had positive results on AFB smear of PBS alone. Additionally, 52 patients (68%) had positive results on mycobacterial culture and 12 (16%) had positive results on mycobacterial culture of PBS exclusively. Therefore, in this study population, a total of 18 patients (20%) were finally diagnosed as having PTB with PBS results only, even though AFB smear microscopy and culture of other specimens had negative results.
PBS could improve the diagnostic yield by 20% when diagnosing pauci-bacillary PTB. In addition, about 8% of the patients could be diagnosed rapidly because of AFB smear microscopy positivity for PBS. Therefore, PBS use should be considered as a complementary diagnostic approach in patients with suspected pauci-bacillary PTB.
Although autologous induced pluripotent stem cells (iPSCs) can potentially be useful for treating patients without immune rejection, in reality it will be extremely expensive and labor‐intensive to ...make iPSCs to realize personalized medicine. An alternative approach is to make use of human leukocyte antigen (HLA) haplotype homozygous donors to provide HLA matched iPSC products to significant numbers of patients. To establish a haplobank of iPSCs, we repurposed the cord blood bank by screening ∼4,200 high resolution HLA typed cord blood samples, and selected those homozygous for the 10 most frequent HLA‐A,‐B,‐DRB1 haplotypes in the Korean population. Following the generation of 10 iPSC lines, we conducted a comprehensive characterization, including morphology, expression of pluripotent markers and cell surface antigens, three‐germ layer formation, vector clearance, mycoplasma/microbiological/viral contamination, endotoxin, and short tandem repeat (STR) assays. Various genomic analyses using microarray and comparative genomic hybridization (aCGH)‐based single nucleotide polymorphism (SNP) and copy number variation (CNV) were also conducted. These 10 HLA‐homozygous iPSC lines match 41.07% of the Korean population. Comparative analysis of HLA population data shows that they are also of use in other Asian populations, such as Japan, with some limited utility in ethnically diverse populations, such as the UK. Taken together, the generation of the 10 most frequent Korean HLA‐homozygous iPSC lines serves as a useful pointer for the development of optimal methods for iPSC generation and quality control and indicates the benefits and limitations of collaborative HLA driven selection of donors for future stocking of worldwide iPSC haplobanks. Stem Cells 2018;36:1552–1566
By repurposing the existing cord blood bank, we established 10 most frequent HLA‐homozygous iPSC lines from the Korean population. Comparative HLA analysis indicates that they are relevant to multiple populations including Japan and the UK. This study highlights the importance of collaborative HLA driven selection of donors for future stocking of worldwide iPSC haplobanks.
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