An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis.

Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production. This results in two molecularly and functionally distinct populations of megakaryocyte progenitors. The age-induced megakaryocyte progenitors have a profoundly enhanced capacity to engraft, expand, restore, and reconstitute platelets in situ and upon transplantation and produce an additional platelet population in old mice. The two pools of co-existing platelets cause age-related thrombocytosis and dramatically increased thrombosis in vivo. Strikingly, aging-enriched platelets are functionally hyper-reactive compared with the canonical platelet populations. These findings reveal stem cell-based aging as a mechanism for platelet dysregulation and age-induced thrombosis.

Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny.

Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades of chromatin remodeling dictate ensuing fate decisions? Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. Oligopotent progenitor populations operating between the HSCs and unipotent cells play essential roles in effecting hematopoietic homeostasis. To test the hypothesis that selective HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during progenitor differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points. Additionally, quantification of genome-wide peak count and size revealed overall greater chromatin accessibility in HSCs, allowing us to identify HSC-unique peaks as putative regulators of self-renewal and multilineage potential. Finally, CRISPRi-mediated targeting of ATACseq-identified putative CREs in HSCs allowed us to demonstrate the functional role of selective CREs in lineage-specific gene expression. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.

Testing a model of benefit-finding and growth in youths with chronic health conditions.

BACKGROUND: The experience of benefit-finding and growth (BFG), defined as perceiving positive life changes resulting from adversity, is increasingly studied among youths with chronic health conditions (CCs). However, empirical evidence is scarce for explaining individual differences in BFG. The study aimed to test a model of BFG, including an interplay of personal and environmental factors and coping processes. METHODS: A sample of N = 498 youths (12-21 years) recruited from three German patient registries for CCs (type 1 diabetes: n = 388, juvenile idiopathic arthritis: n = 82, cystic fibrosis: n = 28) completed a questionnaire including self-reported optimism, social support from parents and peers, coping strategies, and BFG. The model was created to reflect the theoretical assumptions of the Life Crisis and Personal Growth model and current empirical evidence. Structural equation modeling was conducted to evaluate the incremental explanatory power of optimism, peer group integration, parental support, acceptance, cognitive reappraisal, and seeking social support over and above sociodemographic and disease-related characteristics. RESULTS: The model (CFI = 0.93; RMSEA = 0.04; SRMR = 0.05) explained 32% of the variance in BFG. Controlling for sociodemographic and disease-related characteristics, acceptance, cognitive reappraisal, and seeking social support were directly and positively linked to BFG. All tested coping strategies significantly mediated the association between optimism and BFG, whereas seeking social support significantly mediated the relation between peer group integration and BFG. DISCUSSION: The study stresses the prominent role of emotion-focused coping strategies and peer group integration in enhancing BFG in youths with CCs. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00025125. Registered on May 17, 2021.

Electrogelation: Controlled Fast Formation of Micrometer-Thick Films from Low-Molecular Weight Hydrogelators.

The controlled electrochemical deposition of hydrogels from low-molecular weight hydrogelators (LMWHGs) allows for the defined formation of thin films on electrodes. Here, the deposition of fibrillar networks consisting of N,N',N″-tris(4-carboxyphenylene)-1,3,5-benzenetricarboxamide (BTA) onto ultraflat gold electrodes has been studied. This process, also termed electrogelation, is based on a local change in the pH due to electrolysis of water at the electrode. The protonation of the BTA sodium salt leads to self-assembly into supramolecular fibrillar structures mainly via hydrogen bonding of the uncharged molecules. The resulting hydrogel film was characterized in terms of its thickness by atomic force microscopy (AFM). Two different AFM-based techniques have been used: ex situ imaging of dried films and in situ nanoindentation of the hydrated hydrogel films. The deposition process was studied as a function of gelator concentration, applied potential, and gelation time. These parameters allow control of the film thickness to a high degree of accuracy within a few tenths of nanometers. Film formation takes place in a few seconds at moderate applied potentials, which is beneficial for biomedical applications. The results obtained for the BTA presented here can be transferred to any type of pH-responsive LMWHG and many reversibly formed hydrogel films.

The value of cardiac sympathetic activity and mechanical dyssynchrony as cardiac resynchronization therapy response predictors: comparison between patients with ischemic and non-ischemic heart failure.

BACKGROUND: Impaired cardiac sympathetic activity and mechanical dyssynchrony (MD) are associated with poor prognosis in patients with heart failure (HF) after cardiac resynchronization therapy (CRT). The study aims to assess the significance of scintigraphic evaluation of cardiac sympathetic innervation and contractility in predicting response to CRT in patients with ischemic and non-ischemic chronic HF. METHODS AND RESULTS: The study includes 58 HF patients, who were referred for CRT. Prior to CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging and gated myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) SPECT/CT device. At a one-year follow-up post-CRT, the delayed heart-to-mediastinum 123I-MIBG uptake ratio was an independent predictor of CRT response in non-ischemic HF patients (OR 1.469; 95% CI 1.076-2.007, p = .003). In ischemic HF patients the MD index histogram bandwidth (HBW) obtained by CZT-gated MPI had a predictive value (OR 1.06, 95% CI 1.001-1.112, p = .005) to CRT response. CONCLUSION: CRT response can be predicted by cardiac 123I-MIBG scintigraphy, specifically by the heart-to-mediastinum ratio in non-ischemic HF and by the MD index HBW in ischemic HF. These results suggest the value of a potentially useful algorithm to improve outcomes in HF patients who are candidates for CRT.

Multicenter validation of Early Warning Scores for detection of clinical deterioration in COVID-19 hospitalized patients.

Objective: Investigate the predictive value of NEWS2, NEWS-C, and COVID-19 Severity Index for predicting intensive care unit (ICU) transfer in the next 24 h. Design: Retrospective multicenter study. Setting: Two third-level hospitals in Argentina. Patients: All adult patients with confirmed COVID-19, admitted on general wards, excluding patients with non-intubated orders. Interventions: Patients were divided between those who were admitted to ICU and non-admitted. We calculated the three scores for each day of hospitalization. Variables: We evaluate the calibration and discrimination of the three scores for the outcome ICU admission within 24, 48 h, and at hospital admission. Results: We evaluate 13,768 days of hospitalizations on general medical wards of 1318 patients. Among these, 126 (9.5%) were transferred to ICU. The AUROC of NEWS2 was 0.73 (95%CI 0.68-0.78) 24 h before ICU admission, and 0.52 (95%CI 0.47-0.57) at hospital admission. The AUROC of NEWS-C was 0.73 (95%CI 0.68-0.78) and 0.52 (95%CI 0.47-0.57) respectively, and the AUROC of COVID-19 Severity Index was 0.80 (95%CI 0.77-0.84) and 0.61 (95%CI 0.58-0.66) respectively. COVID-19 Severity Index presented better calibration than NEWS2 and NEWS-C. Conclusion: COVID-19 Severity index has better calibration and discrimination than NEWS2 and NEWS-C to predict ICU transfer during hospitalization.

Objetivo: Investigar el valor predictivo de los scores NEWS2, NEWS-C y COVID-19 Severity Index para predecir la transferencia de urgencia a la unidad de cuidados intensivos (UCI) en las próximas 24 horas. Diseño: Estudio multicéntrico retrospectivo. Ámbito: Dos hospitales de tercer nivel en Argentina. Pacientes: Pacientes adultos con COVID-19, ingresados en salas generales, excluyendo pacientes con órdenes de no intubar. Intervenciones: Se dividió a los pacientes entre los que ingresaron en la UCI y los que no ingresaron. Calculamos las tres puntuaciones para cada día de hospitalización. Variables: Evaluamos la calibración y discriminación de las tres puntuaciones para predecir el traslado de urgencia a UCI en las 24, 48 h previas al pase a UCI y al ingreso hospitalario. Resultados: Evaluamos 13.768 días de hospitalización en internación general de 1.318 pacientes, de los cuales 126 (9,5%) fueron trasladados a UCI. El AUROC del NEWS2 fue de 0,73 (IC 95% 0,68-0,78) 24 h antes del ingreso en UCI y de 0,52 (IC 95% 0,47-0,57) al ingreso hospitalario. El AUROC de NEWS-C fue de 0,73 (IC 95% 0,68-0,78) y 0,52 (IC 95% 0,47-0,57) respectivamente, y el AUROC del COVID-19 Severity Index fue de 0,80 (IC 95% 0,77-0,84) y 0,61 (IC 95% 0,58-0,66) respectivamente. El COVID-19 Severity Index presentó una mejor calibración que NEWS2 y NEWS-C. Conclusión: El COVID-19 Severity Index presentó una mejor calibración y discriminación que NEWS2 y NEWS-C para predecir la transferencia de la UCI durante la hospitalización.

Prediction of appropriate ICD therapy in patients with ischemic heart failure.

BACKGROUND: Previous studies show inconsistent results on the role of innervation imaging (with I-123-mIBG) and perfusion imaging in predicting appropriate ICD therapy (aICDth). These studies included patients with both dilated and ischemic cardiomyopathy. This study compared the ability of 123I-mIBG imaging along with perfusion imaging (using thallium-199) to predict aICDth in patients with ischemic heart failure (IHF) in relation to indication for ICD implantation (primary vs. secondary prevention of sudden cardiac death (SCD)). METHODS: mIBG/thallium SPECT imaging were performed before ICD implantation in 80 patients with IHF: 49 candidates for primary and 31 for secondary SCD prevention. RESULTS: During a mean follow-up of 18 months, the imaging results could not predict patients with appropriate ICD therapy among patients with ICD implants for primary SCD prevention. While in the secondary SCD prevention group, those who received a ICDth had significantly larger summed scores of regional perfusion and innervation impairment, but not higher heart-to-mediastinal mIBG ratio. The best results to predict aICDth were using mIBG summed score (cut-off point > 34%, sensitivity 72%, specificity 100%, AUC 0.909, P < 0.0001). CONCLUSION: The prognostic value of innervation and perfusion imaging in patients with IHF differ based on indication for ICD implantation (primary vs. secondary prevention of SCD).

Uterine Sarcoma With FGFR1-TACC1 Gene Fusion: A Case Report and Review of the Literature.

With the growing availability of RNA sequencing technology in the pathology laboratory, new gene fusion-associated malignancies are increasingly being characterized. In this article, we describe the second ever reported case of a uterine sarcoma harboring a FGFR1-TACC1 gene fusion. The patient, a 53-yr-old perimenopausal woman, was found to have a 6 cm mass spanning the lower uterine segment and endocervix. Histologically, this was a spindle cell neoplasm with coagulative necrosis, moderate cytologic atypia, and increased mitotic activity. By immunohistochemistry, the neoplastic cells coexpressed CD34 and S100, and lacked smooth muscle marker expression. RNA sequencing revealed the presence of a FGFR1-TACC1 gene fusion. This report provides further evidence to suggest that FGFR1-TACC1 may be a recurrent fusion in a subset of uterine sarcomas. RNA sequencing using a panel that includes FGFR-TACC family fusions should be considered for uterine sarcomas that do not fit conventional diagnostic criteria, particularly as tumors with these fusions may be amenable to targeted therapy.

Ventricular tachycardia incidence and erythrocyte membranes ß-adrenoreactivity in patients with implanted cardioverter-defibrillator.

BACKGROUND: In patients with high risk of ventricular tachycardia (VT) the proven beneficial therapy is the implantable cardioverter defibrillator (ICD). It has been shown that the coronary artery disease (CAD) and VT development are accompanied by a persistent change of the sympathoadrenal system activity. This leads to a decrease in the total density of the erythrocyte membrane ß-adrenergic receptors. The purpose of this study was to identify the relationship of the erythrocyte membranes ß-adrenoreactivity (EMA) with VT development in patients with CAD and ICD. METHOD: Sixty-three patients (male - 53, age - 66.6 ± 9.2 years) with CAD and ICD were included to the study. EMA was studied using a method for assessing erythrocyte osmoresistance increase as a result of ß-adrenergic receptors blockade by a selective ß-adrenergic blocker. VT and ventricular fibrillation (VF) events recorded by ICD were evaluated. RESULTS: The 1st group consist of 23 patients with VT/VF events recorded by ICD during 27.0 [14.0; 53.0] months follow-up period. EMA indicator in this group was 41.54% [27.15; 51.26]. The 2nd group consist of 40 patients without VT/VF events and the same indicator was significantly higher - 55.42% [35.67; 62.33] (p = .04). The ROC-analysis (AUC = 0.657; Sen = 78.26; Spe = 55.00; p = .031) and binary logistic regression (OR = 0.9679; 95% CI: 0.9384-0.9983; p = .038) showed that EMA indicator 51.26% or lower was the independent predictor of VT events. CONCLUSIONS: In patients with CAD and ICD erythrocyte membranes ß-adrenoreactivity indicator 51.26% or lower is the predictor of VT episodes.

LncRNA Biomarkers of Inflammation and Cancer.

Long noncoding RNAs (lncRNAs) are promising candidates as biomarkers of inflammation and cancer. LncRNAs have several properties that make them well-suited as molecular markers of disease: (1) many lncRNAs are expressed in a tissue-specific manner, (2) distinct lncRNAs are upregulated based on different inflammatory or oncogenic stimuli, (3) lncRNAs released from cells are packaged and protected in extracellular vesicles, and (4) circulating lncRNAs in the blood are detectable using various RNA sequencing approaches. Here we focus on the potential for lncRNA biomarkers to detect inflammation and cancer, highlighting key biological, technological, and analytical considerations that will help advance the development of lncRNA-based liquid biopsies.

EVAR as a treatment option for high-risk nonagenarians with complicated abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a life-threatening disease, with an extremely high risk of death when ruptured. With the increase in life expectancy AAA is becoming more prevalent in aging patients. Elective and emergency procedures in elderly patients with AAA are becoming more common, but the indications for aortic repair and outcomes in geriatric patients are debatable. In our report, we present long-term results of a successful endovascular aortic repair (EVAR) of a ruptured juxtarenal aortic aneurysm complicated by hypovolemia and myocardial infarction in a 92-year-old patient. No endoleaks or bleedings were detected with CT angiography in the post-operative period. After two years following the procedure, the patient is doing well and can take care of himself; there was no disease progression as confirmed by ultrasonography. In conclusion, complicated abdominal aortic aneurysms in nonagenarians can be successfully treated by EVAR with fine long-term results.

Effects of IGFBP3 knockdown on human endometrial mesenchymal stromal cells stress-induced senescence.

Insulin-like growth factor binding protein 3 (IGFBP3) is known for its pleiotropic ability to regulate various cellular processes such as proliferation, apoptosis, differentiation etc. It has recently been shown that IGFBP3 is part of the secretome of senescent human endometrial mesenchymal stromal cells (MESCs) (Griukova et al., 2019) that takes part in paracrine propagation of senescence-like phenotype in MESCs (Vassilieva et al., 2020); however, mechanisms of pro-senescent IGFBP3 action in MESCs remain still unexplored. This study is aimed at elucidating the role of IGFBP3 upregulation in senescent MESCs. IGFBP3 knockdown in MESCs committed to H2O2-induced senescence led to partial abrogation of p21/Rb axis, to elevated ERK phosphorylation and to increase in SA-ß-gal activity. Additionally, MESCs derived from various donors were found to demonstrate different IGFBP3 regulation during stress-induced senescence. Obtained results suggest ambiguous role of IGFBP3 in stress-induced senescence of MESCs.

Key histopathologic features in idiopathic noncirrhotic portal hypertension: an interobserver agreement study and proposal for diagnostic criteria.

Histologic features of idiopathic noncirrhotic portal hypertension (INCPH), loosely termed as obliterative portal venopathy (OPV), are heterogenous, often subtle, and overlap with other entities. To this date, no consensus histopathologic diagnostic criteria have been established for INCPH. For these reasons, rendering a reproducible consensus histologic diagnosis of OPV on a liver biopsy may often be challenging even for experienced hepatopathologists. We report herein a two-phase interobserver agreement study on the diagnosis of OPV and assessed the relative value of histologic features in 104 liver biopsies in distinguishing between INCPH and non-INCPH with the goal to obtain a consensus on specific practical diagnostic criteria. Six hepatopathologists blinded to clinical information and original pathologic diagnosis reviewed internet-based case study sets with high-resolution whole-slide images. The initial interobserver agreement on OPV was expectedly low, but significantly improved (moderate agreement in most categories) upon adopting a consensus view recognizing portal vein sclerosis as the only strong independent histologic predictor for INCPH, and that contrary to the conventional view, aberrant portal/periportal vessels does not significantly contribute to the positive assignment of OPV status. We propose a three-tiered classification with diagnostic criteria to facilitate the histologic assignment of OPV status for the evaluation of INCPH. Furthermore, we have validated the performance of the proposed criteria either based on histology alone or coupled with clinicopathologic correlation. This classification may aid in practical histologic assessment of liver biopsies with or without portal hypertension and help to improve diagnostic consistency and accuracy.

Noncontact characterization of microstructured optical fibers coating in real time.

Functional nanocoatings have allowed hollow-core microstructured optical fibers (HC-MOFs) to be introduced into biosensing and photochemistry applications. However, common film characterization tools cannot evaluate the coating performance in situ. Here we report the all-optical noncontact characterization of the HC-MOF coating in real time. Self-assembled multilayers consisting of inversely charged polyelectrolytes (PEs) are deposited on the HC-MOF core capillary, and a linear spectral shift in the position of the fiber transmission minima with increasing the film thickness is observed as small as ∼1.5-6nm per single PE bilayer. We exemplify the practical performance of our approach by registering an increase in the coating thickness from 6±1 to 11±1nm per PE bilayer with increasing ionic strength in the PE solutions from 0.15 to 0.5 M NaCl. Additionally, we show real-time monitoring of pH-induced coating dissolving. Simplicity and high sensitivity make our approach a promising tool allowing noncontact analysis of the HC-MOF coating which is still challenging for other methods.

Ultrasmooth, biocompatible, and removable nanocoating for hollow-core microstructured optical fibers.

Functional nanocoatings of hollow-core microstructured optical fibers (HC-MOFs) have extended the domain of their applications to biosensing and photochemistry. However, novel modalities typically come with increased optical losses since a significant surface roughness of functional layers gives rise to additional light scattering, restricting the performance of functionalization. Here, the technique that enables a biocompatible and removable nanocoating of HC-MOFs with low surface roughness is presented. The initial functional film is formed by a layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA). The alkaline etching at pH 9 results in the reduction of surface roughness from 26 nm to 3 nm and decreases fiber optical losses by three times. The nanocoating can be fully removed within 7 min of the treatment. Natural biocompatibility of BSA alongside antibacterial and antifouling properties of TA makes the presented nanocoating promising for biophotonic applications.

Liver and Biliary Disease of Pregnancy and Anesthetic Implications: A Review.

Liver and biliary disease complicates pregnancy in varying degrees of severity to the mother and fetus, and anesthesiologists may be asked to assist in caring for these patients before, during, and after birth of the fetus. Therefore, it is important to be familiar with how different liver diseases impact the pregnancy state. In addition, knowing symptoms, signs, and laboratory markers in the context of a pregnant patient will lead to faster diagnosis and treatment of such patients. This review article discusses changes in physiology of parturients, patients with liver disease, and parturients with liver disease. Next, general treatment of parturients with acute and chronic liver dysfunction is presented. The article progresses to specific liver diseases with treatments as they relate to pregnancy. And finally, important aspects to consider when anesthetizing parturients with liver disease are discussed.

A prospective investigation of developmental trajectories of psychosocial adjustment in adolescents facing a chronic condition - study protocol of an observational, multi-center study.

BACKGROUND: Relatively little is known about protective factors and the emergence and maintenance of positive outcomes in the field of adolescents with chronic conditions. Therefore, the primary aim of the study is to acquire a deeper understanding of the dynamic process of resilience factors, coping strategies and psychosocial adjustment of adolescents living with chronic conditions. METHODS/DESIGN: We plan to consecutively recruit N = 450 adolescents (12-21 years) from three German patient registries for chronic conditions (type 1 diabetes, cystic fibrosis, or juvenile idiopathic arthritis). Based on screening for anxiety and depression, adolescents are assigned to two parallel groups - "inconspicuous" (PHQ-9 and GAD-7 < 7) vs. "conspicuous" (PHQ-9 or GAD-7 ≥ 7) - participating in a prospective online survey at baseline and 12-month follow-up. At two time points (T1, T2), we assess (1) intra- and interpersonal resiliency factors, (2) coping strategies, and (3) health-related quality of life, well-being, satisfaction with life, anxiety and depression. Using a cross-lagged panel design, we will examine the bidirectional longitudinal relations between resiliency factors and coping strategies, psychological adaptation, and psychosocial adjustment. To monitor Covid-19 pandemic effects, participants are also invited to take part in an intermediate online survey. DISCUSSION: The study will provide a deeper understanding of adaptive, potentially modifiable processes and will therefore help to develop novel, tailored interventions supporting a positive adaptation in youths with a chronic condition. These strategies should not only support those at risk but also promote the maintenance of a successful adaptation. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00025125 . Registered on May 17, 2021.

Dust-Acoustic Nonlinear Waves in a Nanoparticle Fraction of Ultracold (2K) Multicomponent Dusty Plasma.

The nonlinear dust-acoustic instability in the condensed submicron fraction of dust particles in the low-pressure glow discharge at ultra-low temperatures is experimentally and theoretically investigated. The main discharge parameters are estimated on the basisof the dust-acoustic wave analysis. In particular, the temperature and density of ions, as well as the Debye radius, are determined. It is shown that the ion temperature exceeds the temperature of the neutral gas. The drift characteristics of all plasma fractions are estimated. The reasons for the instability excitation are considered.

Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?

Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.

Chondrogenic differentiation followed IGFBP3 loss in human endometrial mesenchymal stem cells.

Insulin-like growth factor binding protein 3 (IGFBP3) is a multifunctional protein, able either to stimulate the cell growth or to promote apoptosis. In particular, IGFBP3 plays significant role in propagation of stress-induced senescence in human endometrium-derived mesenchymal stem cells (MESCs) (Vassilieva et al., 2020). We undertook CRISPR/Cas9-mediated IGFBP3 knockout in an effort to decelerate stress-induced senescence in MESCs, but, unexpectedly, IGFBP3-knockout MESCs culture acquired chondrocyte-like features, such as cell condensation and aggregation. We revealed that IGFBP3-knockout MESCs completely lost CD73 and CD90 MESCs positive surface markers, and significantly decreased expression of CD105 and CD146 MESCs positive surface markers. In addition, we found IGFBP3-knockout MESCs aggregates positively stained for Alcian Blue. We also detected expression of collagen type II in IGFBP3-knockout MESCs. The obtained results indicate that MESCs lost stemness after IGFBP3-knockout and underwent differentiation toward chondrogenic lineage. Our findings can enlighten IGFBP3 role in regulation of MESCs chondrogenesis.