The diagnostic ability of peripapillary vessel density in primary open-angle glaucoma suspects.

OBJECTIVE: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. METHODS: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. RESULTS: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. CONCLUSION: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

Canalicular laceration repair using a novel bicanalicular silicone stent versus traditional bicanalicular stent with nasal fixation.

PURPOSE: To compare the clinical effects of two types of lacrimal stents in the repair of canalicular lacerations. METHODS: A retrospective analysis was conducted on patients with canalicular lacerations between January 2017 and December 2022. The canalicular reconstruction was performed using either the Runshi-RS bicanalicular silicone stent or the traditional bicanalicular silicone stent with nasal fixation, under a surgical microscope. The stent was placed for 3 months, and patients were followed up for more than 3 months after extubation. The anatomical and functional success rates were compared between the two groups. Anatomical success was assessed through diagnostic probing and irrigation of lacrimal passage, while functional success was determined by the patient's subjective symptoms of epiphora. RESULTS: The study included 315 patients (315 eyes) undergoing canalicular laceration repair. The Runshi-RS stent was utilized in 147 patients (46.7%), while the traditional stent with nasal fixation was employed in 168 patients (53.3%). The anatomical success rates (99.3% vs 98.8%, P = 0.642) and functional success rates (87.2% vs 88.1%, P = 0.926) were similar between the RS group and the traditional stent group. Postoperative complications were fewer (4.1% vs 10.1%, P = 0.04) and the operation time was shorter (67.1 ± 35.3 min vs 86.1 ± 43.4 min, P < 0.001) in the RS group. CONCLUSION: The Runshi-RS tube demonstrates favorable surgical outcomes for the repair of canalicular lacerations. Compared to the traditional stent with nasal fixation, the RS stent allows for shorter operation times and fewer postoperative complications in the repair of canalicular lacerations.

Accuracy of new intraocular lens calculation formulas in Chinese eyes with short axial lengths.

Purpose: To compare the measurement accuracy of new/updated intraocular lens (IOL) power calculation methods, namely, Kane, Emmetropia Verifying Optical (EVO), with existing methods (Barrett Universal II, Olsen, Haigis, Hoffer Q, Holladay 1, SRK/T) in Chinese eyes with axial lengths ≤ 22.5 mm. Methods: The study included data from patients who underwent uneventful cataract surgery with the insertion of ZCB00 IOL. Refractive prediction errors were determined by calculating the difference between postoperative refraction and the predicted refraction using each formula. Various parameters were evaluated, including mean prediction error (ME), mean absolute error (MAE), median absolute error (MedAE), and the percentage of eyes with prediction errors (PE) within different ranges. Results: The study enrolled 38 eyes of 38 patients, and the Barrett Universal II formula demonstrated the lowest MAE and MedAE among the tested formulas. Post hoc analysis using Wilcoxon signed-rank pairwise comparisons for non-parametric samples with Bonferroni correction revealed no significant difference in postoperative refractive prediction among all the formulas (P > 0.05). The percentage of eyes with PE within ± 0.5 D was as follows: Barrett Universal II, 81.58%; Haigis, 78.95%; EVO, 76.32%; Olsen, 76.32%; Holladay I, 73.68%; SRK/T, 71.05%; Kane, 68.42%; and Hoffer Q, 65.79%. Conclusion: The Barrett Universal II formula was more accurate than the other formulas for Chinese eyes with AL ≤ 22.5 mm.

Evaluation and comparison of ocular biometric parameters obtained with Tomey OA-2000 in silicone oil-filled aphakic eyes.

PURPOSE: To evaluate a new non-contact instrument (OA-2000) measuring the ocular biometry parameters of silicone oil (SO)-filled aphakic eyes, as compared with IOLMaster 700. METHODS: Forty SO-filled aphakic eyes of 40 patients were enrolled in this cross-sectional clinical trial. The axial length (AL), central corneal thickness (CCT), keratometry ((flattest keratometry) Kf and (steep keratometry, 90° apart from Kf) Ks), and axis of the Kf (Ax1) were measured with OA-2000 and IOLMaster 700. The coefficient of variation (CoV) was calculated to assess the repeatability. The correlation was evaluated by the Pearson coefficient. Bland-Altman analysis and paired t test were used to analyze the agreements and differences of parameters measured by the two devices, respectively. RESULTS: The mean AL obtained with the OA-2000 was 23.57 ± 0.93 mm (range: 21.50 to 25.68 mm), and that obtained with the IOLMaster 700 was 23.69 ± 0.94 mm (range: 21.85 to 25.86 mm), resulting in a mean offset of 0.124 ± 0.125 mm (p < 0.001). The mean offset of CCT measured by OA-2000 and IOLMaster 700 was 14.6 ± 7.5 µm (p < 0.001). However, the Kf, Ks and Ax1 values from the two devices were comparable (p > 0.05). All the measured parameters of the two devices showed strong linear correlations (all r ≥ 0.966). The Bland-Altman analysis showed a narrow 95% limits of agreement (LoA) of Kf, Ks and AL, but 95%LoA of CCT and Ax1 was wide, which were - 29.3 ~ 0.1 µm and-25.9 ~ 30.7°respectively. The CoVs of the biometric parameters obtained with OA-2000 were lower than 1%. CONCLUSION: In SO-filled aphakic eyes, the ocular parameters (including AL, Kf, Ks, Ax1, and CCT) measured by the OA-2000 and IOLMaster 700 had a good correlation. Two devices had an excellent agreement on ocular biometric measurements of Kf, Ks and AL. The OA-2000 provided excellent repeatability of ocular parameters in SO-filled aphakic eyes.

Preoperative geometric parameters predict the outcome of lamellar keratoscleroplasty in patients with limbal dermoids.

PURPOSE: To find preoperative simple geometric parameters to predict the outcome of lamellar keratoscleroplasty in patients with corneal limbal dermoids. METHODS: We retrospectively analyzed the data of 30 patients with limbal dermoids who underwent lamellar keratoscleroplasty and were followed up for more than 6 months. Seven geometric parameters were used to analyze the relationship with postoperative visual acuity, astigmatism, and scar formation and investigated for their influence on postoperative outcome. These seven parameters included the cornea-invaded area of dermoid, dermoid area, the cornea-invaded length of dermoid, the corneal limbus invaded length of dermoid, dermoid size, bed size, graft size. Furthermore, we divided patients with corneal limbal dermoids into amblyopia group and non-amblyopia group, and analyzed the clinical characteristics of the amblyopia group. RESULTS: The mean age of the patients at surgery was 10.6 ± 5.83 years. The 7 geometric parameters, preoperative and postoperative astigmatism of the amblyopia group were higher than those of the non-amblyopia group (all P < 0.05). Among the geometric parameters analyzed, the r coefficients between the cornea-invaded length of dermoid and postoperative visual acuity and astigmatism were the highest (r = 0.854, r = 0.714). The r coefficient between the corneal limbus invaded length of dermoid and the postoperative scar was the highest (r = 0.375). The r coefficient between age and postoperative steroid-induced high intraocular pressure was the highest (r = - 0.416). In univariate regression analysis, the cornea-invaded length of dermoid was significantly correlated with postoperative visual acuity (ß = 0.270, P < 0.001) and postoperative astigmatism (ß = 1.362, P < 0.001). Among the geometric parameters analyzed, the cornea-invaded length of dermoid had best stratified patients in grouping with or without amblyopia (cutoff > 2.24). CONCLUSION: The cornea-invaded length of dermoid was the most important related factor of postoperative visual acuity, astigmatism, and amblyopia. The corneal limbus invaded length of dermoid was the most important related factor of postoperative scar formation. The geometric parameters and astigmatism in patients with amblyopia were larger than those in patients without amblyopia.

The Topographic Relationship Between Choroidal Microvascular Dropout and Glaucomatous Damage in Primary Angle-Closure Glaucoma.

Purpose: To study the topographic relationship between parapapillary choroidal microvasculature dropout (MvD) and parapapillary retinal nerve fiber layer (RNFL) defect in primary angle-closure glaucoma (PACG) eyes. Methods: This cross-sectional study was carried out in a glaucoma clinic. Patients with PACG and healthy controls were consecutively enrolled. Each subject underwent optical coherence tomography angiography (OCTA) and OCT testing; additionally, visual field (VF) tests were also conducted in the patients with PACG. MvD was determined when choroidal layer images in OCTA showed a complete loss of the microvasculature. The study included 55 patients with PACG and 30 healthy controls. Results: Fifty-five eyes in 55 patients with PACG and 30 eyes in 30 healthy controls were recruited. MvD was found in 26 PACG eyes (47.3%), but no MvD was found in the healthy eyes. Compared with PACG eyes without MvD, eyes with MvD had thinner average RNFL (P < 0.001), worse VF mean deviation (P = 0.006), and lower peripapillary vessel density (P < 0.001). Between MvD and RNFL defects, there was good topographic consistency in angular circumference (Bland-Altman 95% confidence interval [CI], -24.9° to 21.0°) and position (Bland-Altman 95% CI, -18.6° to 20.6°). There was a significant correlation between the MvD angular circumference and the average peripapillary vessel density (r = -0.505; P = 0.014), average RNFL thickness (r = -0.742; P < 0.001), and VF mean deviation (r = -0.572; P = 0.004). Conclusions: In patients with PACG, the MvD angular circumference and position were highly topographic consistent with those of the peripapillary RNFL defect area. This study suggests that there is a significant correlation between MvD and glaucoma optic nerve injury. Translational Relevance: Given the vascular etiology for glaucoma, the current research suggests that the MvD angular circumference may serve as a potential supplementary clue of glaucoma disease severity.

Canalicular laceration repair with a novel bicanalicular silicone tube.

PURPOSE: This study aimed to investigate the efficacy and safety of canalicular laceration repair using a novel bicanalicular silicone tube. METHODS: Retrospective and consecutive patients who underwent canalicular laceration repair using novel Runshi-RS bicanalicular silicone stents from January 2020 to February 2021 were included. The stent was placed for 3 months, and patients were followed up for more than 3 months after extubation. Demographics, causes of eyelid injuries, placement time and position of stent, and surgical outcomes at follow-up were recorded. Anatomical success was evaluated by diagnostic probing and irrigation of lacrimal passage, while functional success was evaluated by the patient's subjective symptoms of epiphora. RESULTS: This study included 43 patients with canalicular laceration. The median age was 43 years (3-75 years). The average duration of stent implantation was 12.9 weeks, and the follow-up time was 8.8 months. No complications were observed in any patients during operation and follow-up. After extubation, irrigation of the lacrimal passage in 43 eyes showed no obstruction, and the anatomical success rate was 100%. Overall, 39 patients (90.7%) had no subjective symptoms of epiphora. All patients got good cosmetic results. Furthermore, subgroup classification showed deep laceration group (distance from laceration to punctum>5 mm) accounted for 51.2%, and the functional success rate of the deep laceration group was lower than that of the shallow laceration group. CONCLUSION: Runshi-RS bicanalicular silicone stent achieved good anatomical (100%) as well as functional (90.7%) success and good cosmetic results (100%) in patients with canalicular laceration repair.

Surgical Resection of Dorsal Spinal Meningiomas with the Inner Dura Layer-An Improved Preservation Technique of Spinal Dura in 40 Cases.

BACKGROUND: Spinal meningiomas are the common benign tumors in intradural extramedullary spinal tumors. Simpson grade I resection is recommended to avoid tumor recurrence. However, the dura reconstruction increases a risk of cerebrospinal fluid leakage after this surgical resection. To address this concern, the inner dura layer resection and long-term surgical outcomes of this technique were designed and examined after total tumor resection to preserve the outer dura layer. METHODS: This study included 40 spinal meningioma patients undergoing the outer dura layer resection between 2002 and 2019. Clinical characteristics, radiologic features, preoperative and postoperative functional states, tumor recurrence, and perioperative complications were described and evaluated. RESULTS: A total of 40 spinal meningioma cases with the median age of 63 years (36-81 years) were enrolled in this study. The median postoperative follow-up period of all 40 cases was 96 months (34-193 months). About 82.5% of cases were located in the thoracic spine, while 16.5% of cases were located in the cervical spine. Of the symptomatic cases, 87.5% of cases follow with satisfactory outcomes and 12.5% of cases follow with unexpected outcomes. The local spinal meningioma recurrence rate was 2.5% (1 of 40 cases). No postoperative cerebrospinal fluid leak occurred in the 40 spinal meningioma cases. CONCLUSIONS: A long-term postoperative follow-up indicated that this modified spinal dura preservation technique caused good neurologic improvement with rare recurrence. Therefore we recommend this improved technique may be an alternative surgical option for total resection of spinal meningiomas with favorable prognosis.

Spatial positional relationship between macular superficial vessel density and ganglion cell-inner plexiform layer thickness in primary angle closure glaucoma.

PURPOSE: To evaluate the spatial relationship between macular superficial vessel density (SVD) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in primary angle closure glaucoma (PACG), and to investigate diagnostic abilities of macular SVD and foveal avascular zone (FAZ) parameters. METHODS: This was a cross-sectional study on 38 PACG patients (38 eyes) and 25 healthy subjects (25 eyes). Macular region was imaged using a 1050-nm-wavelength swept-source optical coherence tomography (OCT) angiography (OCTA) system (DRI OCT Triton, TOPCON). Vessel density of the macular region was quantified by ImageJ software. The peripapillary retinal nerve fiber layer (pRNFL) thicknesses and macular GCIPL thickness were obtained by swept-source OCT. Pearson correlation analysis was used to evaluate the spatial positional relationship between macular SVD and macular GCIPL thickness. At the same time, the correlation between macular SVD and pRNFL thickness was evaluated. Areas under the receiver operating characteristics curves (AUCs) of OCT, OCTA and FAZ measurement metrics were calculated to assess the diagnostic ability for glaucoma. RESULTS: Macular GCIPL thickness had a moderate correlation with the macular SVD in the inferonasal sector (r = 0.426, P = 0.008). In addition, there was a strong correlation between inferonasal sector of macular vessel density and 5,6,7,8 clock-hour regions of the pRNFL thicknesses (all r > 0.5). Inferoinferior sector of macular SVD and 6,7 clock-hour regions of pRNFL thicknesses also had strong correlation (all r > 0.5). The AUCs of macular SVD ranged between 0.61 (superonasal sector) and 0.76 (inferoinferior sector). The FAZ circularity index showed the highest diagnostic power (AUC = 0.94;95% CI, 0.85-0.99), followed by superotemporal sector of macular GCIPL thicknesses (0.93;95% CI,0.83-0.98). CONCLUSIONS: Sector of macular SVD not only had a spatial positional correlation with corresponding macular GCIPL thickness, but also with clock-hour regional pRNFL thicknesses in PACG eyes. FAZ circulation index might be a useful diagnostic parameter.

Peripapillary vessel density measurement of quadrant and clock-hour sectors in primary angle closure glaucoma using optical coherence tomography angiography.

BACKGROUND: The purpose of this study was to investigate diagnostic ability of peripapillary vessel density of primary angle closure glaucoma (PACG) eyes in quadrant and clock-hour sectors by optical coherence tomography angiography (OCTA). METHODS: This was a cross-sectional study on forty-one PACG patients (41eyes) and twenty-seven healthy subjects (27 eyes). All subjects underwent OCTA (DRI OCT Triton; Topcon Corporation, Tokyo, Japan) and peripapillary retinal nerve fiber layer (RNFL) thickness imaging with swept-source optical coherence tomography (OCT). The peripapillary vessel density of quadrant and clock-hour sectors was quantified by imageJ software. The diagnostic capability of OCTA and OCT parameters was evaluated by the areas under the receiver operating characteristics curves (AUCs). Pearson correlation analysis or Spearman correlation test was used to evaluate the correlation between vessel density parameters and related factors. RESULTS: Compared with the control group, the peripapillary vessel density of glaucomatous group was lower to different degrees in the four quadrants and each clock-hour sectors, and vessel density reduced most at 7 o'clock. The difference between the diagnostic ability of peripapillary vessel density and peripapillary RNFL thickness was not statistically significant, except 4 o'clock and inferior quadrant. The inferior quadrant peripapillary vessel density had the best diagnostic value (AUC0.969), followed by the 7 o'clock vessel density (AUC0.964), average vessel density (AUC0.939) and the 7 o'clock RNFL thickness (AUC0.919). The average peripapillary vessel density was correlated with average RNFL and visual field (VF) mean deviation (P < 0.001). CONCLUSIONS: In PACG, the diagnostic ability of the peripapillary vessel density is equivalent to the peripapillary RNFL thickness. Understanding spatial characteristics of the peripapillary vessel density in PACG may be helpful for clinical diagnosis and monitoring the progress of diseases.

Human pluripotent stem cell-derived mesenchymal stem cells prevent chronic allergic airway inflammation via TGF-ß1-Smad2/Smad3 signaling pathway in mice.

BACKGROUND: Asthma is a chronic disease involving inflamed airways, which were previously demonstrated, can be modulated by the mesenchymal stem cells derived from induced pluripotent stem cells (iPSC-MSCs). However, the long-term effects of iPSC-MSCs in inflamed airways are still unidentified. This study investigated the long-term effects and potential mechanisms involved in the immunomodulatory effects of iPSC-MSCs in the chronic mouse asthma model. METHODS: Both human iPSC-MSCs and bone marrow (BM)-MSCs were transplanted into the long-term ovalbumin-induced mice before sensitization phase or during the challenge phase. Airway hyper-respnsiveness measurement, immunohistochemistry and ELISA were employed to assess the effects of MSCs. In addition, Smad2/3 levels were assessed by western blot analysis to investigate the possible mechanism involved. RESULTS: The systemic administration of human iPSC-MSCs before the challenge protected the mice from the characters of the chronic allergic airway inflammation, in particular improving the airway remodeling and preventing fibrosis. In addition, the TGF-ß1/Smad pathway was identified involved in the immunomodulatory effects of iPSC-MSCs on chronic allergic airway inflammation. CONCLUSIONS: The study demonstrated that iPSC-MSCs are capable of preventing chronic allergic airway inflammation over a prolonged period, which further proved the iPSC-MSC therapeutic potential for allergic airway inflammation in a clinical scenario.

Accuracy of lateral cephalogram for diagnosis of adenoid hypertrophy and posterior upper airway obstruction: A meta-analysis.

INTRODUCTION: Accurate diagnosis of adenoid hypertrophy and posterior upper airway obstruction using a lateral cephalogram is challenging. No universal guidelines for assessing adenoidal enlargement and upper airway obstruction have been established. We performed a meta-analysis to assess the diagnostic accuracy of a lateral cephalogram for adenoid hypertrophy. METHODS: After searching a wide range of electronic databases and screening titles and abstracts, we evaluated full papers describing potentially eligible studies according to predefined inclusion criteria. Quality assessment was conducted by adapting the Quality Assessment of Diagnostic Accuracy Studies-2 checklist, and a 2 × 2 contingency table was constructed based on these results. Two authors independently judged the studies and extracted the data. The diagnostic accuracy of a lateral cephalogram for adenoid hypertrophy and posterior upper airway obstruction was calculated using a bivariate meta-analysis model. The Q-test and I2 index were used to test the heterogeneity. RESULTS: Nine studies were included in the meta-analysis. The pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio were 0.86 [95% confidence interval (CI): 0.76-0.92], 0.59 (95% CI: 0.42-0.73), 9.00 (95% CI: 5-17), 2.1 (95% CI: 1.5-3.0), and 0.24 (95% CI: 0.15-0.37), respectively. The area under the summary receiver operator characteristic curve was 0.83 (95% CI: 0.80-0.86). Meta-regression analysis revealed that the sample size and study design significantly contributed to the heterogeneity of sensitivity. CONCLUSIONS: Our findings suggest that the lateral cephalogram exhibits very good diagnostic accuracy (area under the curve: 0.86) for the diagnosis of adenoid hypertrophy and posterior upper airway obstruction. Nevertheless, the rate of false-positive diagnoses should be further considered.

MicroRNA-21 Mediates the Protective Effects of Mesenchymal Stem Cells Derived from iPSCs to Human Bronchial Epithelial Cell Injury Under Hypoxia.

Airway epithelial cell injury is a key triggering event to activate allergic airway inflammation, such as asthma. We previously reported that administration of mesenchymal stem cells (MSCs) significantly alleviated allergic inflammation in a mouse model of asthma, and the mmu-miR-21/ACVR2A axis may be involved. However, whether MSCs protect against bronchial epithelial cell injury induced by hypoxia, and the underlying mechanism, remain unknown. In our study, the human bronchial epithelial cell line BEAS-2B was induced to undergo apoptosis with a hypoxia mimic of cobalt chloride (CoCl2) damage. Treatment of MSCs derived from induced pluripotent stem cells (iPSCs) significantly decreased apoptosis of BEAS-2B cells. There was high miR-21 expression in injured BEAS-2B cells after MSC treatment. Transfection of the miR-21 mimic significantly decreased apoptosis of BEAS-2B, and transfection of a miR-21 inhibitor significantly increased apoptosis. More importantly, the protective effects of MSCs on injured BEAS-2B were reversed by transfection of the miR-21 inhibitor. Binding sites of human miR-21 were identified in the 3'UTR of human ACVR2A. We further determined that CoCl2 stimulation increased ACVR2A expression at both the mRNA and protein levels. Moreover, transfection of the miR-21 mimic further up-regulated ACVR2A expression induced by CoCl2, whereas transfection of the miR-21 inhibitor down-regulated ACVR2A expression. In addition, MSCs increased ACVR2A expression in BEAS-2B cells; however, this effect was reversed after transfection of the miR-21 inhibitor. Our data suggested that MSCs protect bronchial epithelial cells from hypoxic injury via miR-21, which may represent an important target. These findings suggest the potentially wide application of MSCs for epithelial cell injury during hypoxia.

Human iPSC-MSCs prevent steroid-resistant neutrophilic airway inflammation via modulating Th17 phenotypes.

BACKGROUND: Human induced pluripotent stem cells-derived mesenchymal stem cells (iPSC-MSCs) have been shown to be effective in Type 2 helper T cells (Th2)-dominant eosinophilic allergic airway inflammation. However, the role of iPSC-MSCs in Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation remains poorly studied. Therefore, this study was to explore the effects of iPSC-MSCs on an experimental mouse model of steroid-resistant neutrophilic airway inflammation and further determine the underlying mechanisms. METHODS: A mouse model of neutrophilic airway inflammation was established using ovalbumin (OVA) and lipopolysaccharide (LPS). Human iPSC-MSCs were systemically administered, and the lungs or bronchoalveolar lavage fluids (BALF) were collected at 4 h and 48 h post-challenge. The pathology and inflammatory cell infiltration, the T helper cells, T helper cells-associated cytokines, nuclear transcription factors and possible signaling pathways were evaluated. Human CD4+ T cells were polarized to T helper cells and the effects of iPSC-MSCs on the differentiation of T helper cells were determined. RESULTS: We successfully induced the mouse model of Th17 dominant neutrophilic airway inflammation. Human iPSC-MSCs but not dexamethasone significantly prevented the neutrophilic airway inflammation and decreased the levels of Th17 cells, IL-17A and p-STAT3. The mRNA levels of Gata3 and RORγt were also decreased with the treatment of iPSC-MSCs. We further confirmed the suppressive effects of iPSC-MSCs on the differentiation of human T helper cells. CONCLUSIONS: iPSC-MSCs showed therapeutic potentials in neutrophilic airway inflammation through the regulation on Th17 cells, suggesting that the iPSC-MSCs could be applied in the therapy for the asthma patients with steroid-resistant neutrophilic airway inflammation.

The genes involved in asthma with the treatment of human embryonic stem cell-derived mesenchymal stem cells.

BACKGROUND: Asthma is affecting more than 300 million people worldwide, which represents the most common chronic disease among children. We previously found that mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) modulated the immune response on Th2-mediated asthma in vivo and in vitro. This study further evaluated the immunomodulatory effects of MSCs from human embryonic stem cells (hESCs) on asthma. METHODS: Multipotent hESC-MSCs were obtained using a feeder-free method. The hESC-MSCs were analysed for the expression of stem cell surface markers by flow cytometry, their differentiation potentials were analysed using in vitro trilineage differentiation methods hESC-MSCs were transplanted into the murine model with ovalbumin (OVA)-induced airway allergic inflammation. The expression levels of allergic related genes were measured by the mRNA PCR arrays. RESULTS: The hESC-MSCs expressed classical MSC markers and held the capability of differentiation into multiple mesoderm-type cell lineages. hESC-MSCs were able to suppress allergic inflammation by modulating Th2 cells and eosinophils in the mice, and reversed the reduction of regulatory T cells. By using PCR array, 5 mRNAs- chemokine (C-C motif) ligand 11 (Ccl11), Ccl24, interleukin13 (Il13), Il33 and eosinophil-associated, ribonuclease A family, member 11 (Ear11) were identified the most relevant in murine airway allergic inflammation and hESC-MSCs treatment. CONCLUSIONS: The therapeutic effects of hESC-MSCs were identified in the murine model of airway allergic inflammation with key mRNAs involved. This study will provide a better understanding regarding the mechanisms underlying hESC-MSCs therapeutic application in airway allergic inflammation.