Publications by authors named "Mehdi Abbasi"

74 Publications

Red Blood Cells Under Flow Show Maximal ATP Release for Specific Hematocrit.

Biophys J 2021 Sep 18. Epub 2021 Sep 18.

Univ. Grenoble Alpes, CNRS, LIPhy, F-38000 Grenoble, France. Electronic address:

ATP release by red blood cells (RBCs) under shear stress (SS) plays a pivotal role in endothelial biochemical signaling cascades. The aim of this study is to investigate through numerical simulation how does RBCs spatio-temporal organization depend on flow and geometrical conditions to generate ATP patterns. Numerical simulations were conducted in a straight channel by considering both plasma and explicit presence of RBCs, their shape deformation and cell-cell interaction, as well as ATP release by RBCs. Two ATP release pathways through cell membrane are taken into account, pannexin 1 channel (Px1), sensitive to SS, and cystic fibrosis transmembrane conductance regulator (CFTR) which responds to cell deformation. Several flow and hematocrit conditions are explored. The problem is solved by lattice Boltzmann method. Application of SS to the RBC suspension triggers a nontrivial spatial RBC organization and ATP patterns. ATP localizes preferentially in the vicinity of cell-free layer close to channel wall. Conditions for maximal ATP release per cell are identified, which depend on vessel size and hematocrit Ht. Increasing further Ht beyond optimum enhances the total ATP release but should degrade oxygen transport capacity, a compromise between an efficient ATP release and minimal blood dissipation. Moreover, ATP is boosted in capillaries suggesting a vasomotor activity coordination throughout the resistance network.
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http://dx.doi.org/10.1016/j.bpj.2021.09.025DOI Listing
September 2021

Factors Affecting Vagus Nerve Stimulation Outcomes in Epilepsy.

Neurol Res Int 2021 3;2021:9927311. Epub 2021 Aug 3.

General Surgery Department, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Epilepsy as a common neurological disease is mostly managed effectively with antiepileptic medications. One-third of patients do not respond to medical treatments requiring alternative therapies. Vagus nerve stimulation (VNS) has been used in the last decades for the treatment of medically resistant epilepsy. Despite the extensive use of VNS in these patients, factors associated with clinical outcomes of VNS remain to be elucidated. In this study, we evaluated factors affecting VNS outcomes in epileptic patients to have a better understanding of patients who are better candidates for VNS therapy. Several databases including PubMed, Scopus, and Google Scholar were searched through June 2020 for relevant articles. The following factors were assessed in this review: previous surgical history, age at implantation and gender, types of epilepsy, duration of epilepsy, age at epilepsy onset, frequency of attacks, antiepileptic drugs, VNS parameters, EEG findings, MRI findings, and biomarkers. Literature data show that nonresponder rates range between 25% and 65%. Given the complexity and diversity of factors associated with response to VNS, more clinical studies are needed to establish better paradigm for selection of patients for VNS therapy.
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http://dx.doi.org/10.1155/2021/9927311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357517PMC
August 2021

In Vitro Study of Blood Clot Identification and Composition Assessment by Different Magnetic Resonance Sequences.

Cureus 2021 Jul 7;13(7):e16229. Epub 2021 Jul 7.

Neuroradiology, Mayo Clinic, Rochester, USA.

Background Growing data suggest that clot composition can impact revascularization outcomes and can potentially guide treatment strategies for stroke patients with large vessel occlusion. We performed an in vitro study to determine which magnetic resonance (MR) signaling characteristics correlate with clot compositions. Methodology A total of 25 clot analogs were prepared by mixing human plasma and red blood cells (RBCs) with five different combinations (five samples for each combination), namely, Group A, fibrin-rich (95% plasma:5% RBCs); Group B, fibrin-rich (75% plasma:25% RBCs); Group C, intermediate (50% plasma:50% RBCs); Group D, RBC-rich (25% plasma:75% RBCs), and Group E, RBC-rich (5% plasma:95% RBCs). The prepared samples were then scanned with quantitative T2* mapping, T2 fast spin-echo (FSE), T2 gradient-echo (GRE), fluid-attenuated inversion recovery (FLAIR), and susceptibility-weighted angiography (SWAN). Thrombus-T2* relaxation time (TT2*RT) and signal intensity (SI) from different scanning sequences were measured in all groups. SIs between different groups were compared using a one-way analysis of variance. Correlation between TT2*RT and SI was determined using the Pearson correlation test. Results The average TT2*RT decreased from 126 ms to 37 ms from fibrin-rich to RBC-rich clots (Groups A to E). Mean SIs of Groups D and E were lower than Groups A, B, and C on T2 mapping, T2 FSE, T2 GRE, FLAIR, and SWAN images (p < 0.00001). TT2*RT and SI were positively correlated on T2 mapping (R = 0.9628, p = 0.009). Conclusion Different compositions of blood clots can show different TT2*RT and SI on MR imaging. Quantitative T2* mapping and multicontrast MR scanning can help in the characterization of clots causing large vessel occlusion, which is useful to establish treatment strategies for stroke patients.
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http://dx.doi.org/10.7759/cureus.16229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343555PMC
July 2021

Mechanisms of fibrinolysis resistance and potential targets for thrombolysis in acute ischaemic stroke: lessons from retrieved stroke emboli.

Stroke Vasc Neurol 2021 Jul 26. Epub 2021 Jul 26.

Radiology, Mayo Clinic, Rochester, Minnesota, USA.

There has been growing interest and insight into the histological composition of retrieved stroke emboli. One of the main focuses of the stroke clot analysis literature has been the implications of clot composition on mechanical thrombectomy procedures. However, the holy grail of clot analysis may not be in the field of clot-device interaction, but rather, in understanding mechanisms of fibrinolysis resistance. The mechanisms underlying the low response to fibrinolytic therapy, even with the newer, more powerful agents, remain poorly understood. While factors such as embolus size, location and collateral status influence alteplase delivery and recanalisation rates; compositional analyses focused on histological and ultrastructural characteristics offer unique insights into mechanisms of alteplase resistance. In this review, we strive to provide comprehensive review of current knowledge on clot composition and ultrastructural analyses that help explain resistance to fibrinolysis.
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http://dx.doi.org/10.1136/svn-2021-001032DOI Listing
July 2021

Per-pass analysis of recanalization and good neurological outcome in thrombectomy for stroke: Systematic review and meta-analysis.

Interv Neuroradiol 2021 Jul 6:15910199211028342. Epub 2021 Jul 6.

Department of Neurosurgery, Mayo Clinic, Rochester, USA.

Background And Aim: First pass effect (FPE) is defined as achieving a complete recanalization with a single thrombectomy device pass. Although clinically desired, FPE is reached in less than 30% of thrombectomy procedures. Multiple device passes are often necessary to achieve successful or complete recanalization. We performed a systematic review and meta-analysis to determine the recanalization rate after each pass of mechanical thrombectomy and its association with good neurological outcome.

Methods: A literature search was performed for studies reporting the number of device passes required for either successful (mTICI 2b or higher) or complete (mTICI 2c or higher) recanalization. Using random-effect meta-analysis, we evaluated the likelihood of recanalization and good neurological outcome (measured with the modified Rankin Score <2 at 90 days) after each device pass.

Results: Thirteen studies comprising 4197 patients were included. Among cases with failed first pass, 24% of them achieved final complete recanalization and 45% of them achieved final successful recanalization. Independently to the total number of previously failed attempts, the likelihood of achieving successful recanalization was 30% per pass, and the likelihood to achieve complete recanalization was about 20% per pass. The likelihood of good neurological outcome in patients with final successful recanalization decreased after each device pass: 55% after the first pass, 48% after the second pass, 42% after the third pass, 36% after the fourth pass, and 26% for 5 passes or more.

Conclusion: Each pass is associated with a stable likelihood of recanalization but a decreased likelihood of good neurological outcome.
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http://dx.doi.org/10.1177/15910199211028342DOI Listing
July 2021

Endoluminal flow diverters in the treatment of sidewall and bifurcation aneurysm: A systematic review and meta-analysis of complications and angiographic outcomes.

Interv Neuroradiol 2021 Jun 22:15910199211026713. Epub 2021 Jun 22.

Department of Radiology, Mayo Clinic, Rochester, MN, USA.

Background And Aim: The use of endoluminal flow diversion in bifurcation aneurysms has been questioned due to the potential for complications and lower occlusion rates. In this study we assessed outcomes of endovascular treatment of intracranial sidewall and bifurcation aneurysms with flow diverters.

Methods: In July 2020, a literature search for all studies utilizing endoluminal flow diverter treatment for sidewall or bifurcation aneurysms was performed. Data were collected from studies that met our inclusion/exclusion criteria by two independent reviewers and confirmed by a third reviewer. Using random-effects meta-analysis the target outcomes including overall complications (hematoma, ischemic events, minor ischemic stroke, aneurysm rupture, side vessel occlusion, stenosis, thrombosis, transient ischemic stroke, and other complications), perioperative complications, and follow-up (long-term) aneurysm occlusion were intestigated.

Results: Overall, we included 35 studies with 1084 patients with 1208 aneurysms. Of these aneurysms, 654 (54.14%) and 554 (45.86%) were classified as sidewall and bifurcation aneurysm, respectively, based on aneurysm location. Sidewall aneurysms had a similar total complication rate (R) of 27.12% (95% CI, 16.56%-41.09%), compared with bifurcation aneurysms (R, 20.40%, 95% CI, 13.24%-30.08%) (p = 0.3527). Follow-up angiographic outcome showed comparable complete occlusion rates for sidewall aneurysms (R 69.49%; 95%CI, 62.41%-75.75%) and bifurcation aneurysms (R 73.99%; 95% CI, 65.05%-81.31%; p = 0.4328).

Conclusions: This meta-analysis of sidewall and bifurcation aneurysms treated with endoluminal flow diverters demonstrated no significant differences in complications or occlusion rates. These data provide new information that can be used as a benchmark for comparison with emerging devices for the treatment of bifurcation aneurysms.
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http://dx.doi.org/10.1177/15910199211026713DOI Listing
June 2021

Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy.

J Neurointerv Surg 2021 May 11. Epub 2021 May 11.

Department of Neurology, Grady Memorial Hospital, Atlanta, Georgia, USA.

Background: Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine.

Objective: To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots.

Methods: As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells).

Results: MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1-4] vs 1 [1-3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI.

Conclusions: Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.
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http://dx.doi.org/10.1136/neurintsurg-2021-017310DOI Listing
May 2021

e-ASPECTS software improves interobserver agreement and accuracy of interpretation of aspects score.

Interv Neuroradiol 2021 Apr 14:15910199211011861. Epub 2021 Apr 14.

Department of Radiology, Mayo Clinic, Rochester, MN, USA.

Introduction: There is increased interest in the use of artificial intelligence-based (AI) software packages in the evaluation of neuroimaging studies for acute ischemic stroke. We studied whether, compared to standard image interpretation without AI, Brainomix e-ASPECTS software improved interobserver agreement and accuracy in detecting ASPECTS regions affected in anterior circulation LVO.

Methods: We included 60 consecutive patients with anterior circulation LVO who had TICI 3 revascularization within 60 minutes of their baseline CT. A total of 16 readers, including senior neuroradiologists, junior neuroradiologists and vascular neurologists participated. Readers interpreted CT scans on independent workstations and assessed final ASPECTS and evaluated whether each individual ASPECTS region was affected. Two months later, readers again evaluated the CT scans, but with assistance of e-ASPECTS software. We assessed interclass correlation coefficient for total ASPECTS and interobserver agreement with Fleiss' Kappa for each ASPECTS region with and without assistance of the e-ASPECTS. We also assessed accuracy for the readers with and without e-ASPECTS assistance. In our assessment of accuracy, ground truth was the 24 hour CT in this cohort of patients who had prompt and complete revascularization.

Results: Interclass correlation coefficient for total ASPECTS without e-ASPECTS assistance was 0.395, indicating fair agreement compared, to 0.574 with e-ASPECTS assistance, indicating good agreement (P < 0.01). There was significant improvement in inter-rater agreement with e-ASPECTS assistance for each individual region with the exception of M6 and caudate. The e-ASPECTS software had higher accuracy than the overall cohort of readers (with and without e-ASPECTS assistance) for every region except the caudate.

Conclusions: Use of Brainomix e-ASPECTS software resulted in significant improvements in inter-rater agreement and accuracy of ASPECTS score evaluation in a large group of neuroradiologists and neurologists. e-ASPECTS software was more predictive of final infarct/ASPECTS than the overall group interpreting the CT scans with and without e-ASPECTS assistance.
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http://dx.doi.org/10.1177/15910199211011861DOI Listing
April 2021

Per pass analysis of thrombus composition retrieved by mechanical thrombectomy.

Interv Neuroradiol 2021 Apr 7:15910199211009119. Epub 2021 Apr 7.

Departments of Radiology and Neurosurgery, Northwestern University, Chicago, IL, USA.

Background And Aim: Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT.

Methods: Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software.

Results: 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05).

Conclusion: Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.
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http://dx.doi.org/10.1177/15910199211009119DOI Listing
April 2021

Proteomic Analysis of Cardioembolic and Large Artery Atherosclerotic Clots Using Reverse Phase Protein Array Technology Reveals Key Cellular Interactions Within Clot Microenvironments.

Cureus 2021 Feb 22;13(2):e13499. Epub 2021 Feb 22.

Neuroradiology, Mayo Clinic, Rochester, USA.

Thrombus characteristics are dependent on clot composition, but identification of the etiology based on histological analysis has proved inconclusive. Identification of proteomic signatures may help to differentiate between clots of different etiologies such as cardioembolic, large artery atherosclerotic, and other known etiologies, information that could enhance an individualized medicine approach to secondary stroke prevention. In this study, total protein extracts from cardioembolic (n=25) and large artery atherosclerotic (n=23) thrombus specimens were arrayed in quadruplicate on nitrocellulose slides and immunostained for 31 proteins using a Dako Autostainer (Agilent Technologies, Inc., Santa Clara, USA). We quantified 31 proteins involved in platelet and/or endothelial function, inflammation, oxidative stress, and metabolism. Pathway analysis showed more heterogeneity and protein network interactions in the cardioembolic clots but no specific correlations with clot etiology. Reverse-phase protein arrays are a powerful tool for assessing cellular interactions within the clot microenvironment and may enhance understanding of clot formation and origination. This tool could be further explored to help in identifying stroke etiology in large vessel occlusion patients with embolic stroke of an undetermined source.
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http://dx.doi.org/10.7759/cureus.13499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990677PMC
February 2021

Preclinical testing platforms for mechanical thrombectomy in stroke: a review on phantoms, in-vivo animal, and cadaveric models.

J Neurointerv Surg 2021 Sep 15;13(9):816-822. Epub 2021 Mar 15.

Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA

Preclinical testing platforms have been instrumental in the research and development of thrombectomy devices. However, there is no single model which fully captures the complexity of cerebrovascular anatomy, physiology, and the dynamic artery-clot-device interaction. This article provides a critical review of phantoms, in-vivo animal, and human cadaveric models used for thrombectomy testing and provides insights into the strengths and limitations of each platform. Articles published in the past 10 years that reported thrombectomy testing platforms were identified. Characteristics of each test platform, such as intracranial anatomy, artery tortuosity, vessel friction, flow conditions, device-vessel interaction, and visualization, were captured and benchmarked against human cerebral vessels involved in large-vessel occlusion stroke. Thrombectomy phantoms have been constructed from silicone, direct 3D-printed polymers, and glass. These phantoms represent oversimplified patient-specific cerebrovascular geometry but enable adequate visualization of devices and clots under appropriate flow conditions. They do not realistically mimic the artery-clot interaction. For the animal models, arteries from swine, canines, and rabbits have been reported. These models can reasonably replicate the artery-clot-device interaction and have the unique value of evaluating the safety of thrombectomy devices. However, the vasculature geometries are substantially less complex and flow conditions are different from human cerebral arteries. Cadaveric models are the most accurate vascular representations but with limited access and challenges in reproducibility of testing conditions. Multiple test platforms should be likely used for comprehensive evaluation of thrombectomy devices. Interpretation of the testing results should take into consideration platform-specific limitations.
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http://dx.doi.org/10.1136/neurintsurg-2020-017133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364863PMC
September 2021

Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology.

J Neurointerv Surg 2021 Jul 15;13(7):594-598. Epub 2021 Mar 15.

Neurosurgery, Baptist Medical Center Jacksonville, Jacksonville, Florida, USA.

Background: We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ test for categorical variables.

Results: 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%).

Conclusions: Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.
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http://dx.doi.org/10.1136/neurintsurg-2020-017167DOI Listing
July 2021

The Germ Cell-Specific Markers ZPBP2 and PGK2 in Testicular Biopsies Can Predict the Presence as well as the Quality of Sperm in Non-obstructive Azoospermia Patients.

Reprod Sci 2021 05 28;28(5):1466-1475. Epub 2021 Jan 28.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

To assess the role of three testis-specific genes including ZPBP2, PGK2, and ACRV1 in the prediction of sperm retrieval result and quality of retrieved sperm by microdissection testicular sperm extraction (micro-TESE) in non-obstructive azoospermia (NOA) patients. This was a case-control study including 57 testicular samples of NOA patients including 32 patients with successful sperm retrieval (NOA+) and 25 patients with failed sperm retrieval (NOA-), and 9 samples of men with normal spermatogenesis in the testes as the positive control (OA). We investigated the expression of candidate genes by RT-qPCR and germ cell population patterns by DNA flow cytometry in testicular biopsy samples. The association between PGK2 expressions with the quality of retrieved spermatozoa was also evaluated. The RT-qPCR data revealed a significantly higher expression of ZPBP2 and PGK2 in the NOA+ in comparison to NOA- group (P = 0.002, and P = 0.002, respectively). Flow cytometry results revealed that the haploid cell percentage was significantly higher in NOA+ vs. NOA- group (P = 0.0001). In samples with a higher percentage of haploid cells, expression levels of ZPBP2 and PGK2 were higher (P = 0.001). The PGK2 expression was significantly associated with retrieved sperm quality (P = 0.01). Our results contribute to the search for the biomarkers for predicting the presence of testicular sperm and would be useful to avoid unnecessary multiple micro-TESE. Overall, the expression pattern of the ZPBP2 and PGK2 may be useful in predicting sperm recovery success and quality of retrieved sperm in NOA patients.
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http://dx.doi.org/10.1007/s43032-020-00427-9DOI Listing
May 2021

Systematic review and meta-analysis of current rates of first pass effect by thrombectomy technique and associations with clinical outcomes.

J Neurointerv Surg 2021 Mar 13;13(3):212-216. Epub 2021 Jan 13.

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

Background: First pass effect (FPE) in mechanical thrombectomy is thought to be associated with good clinical outcomes.

Objective: To determine FPE rates as a function of thrombectomy technique and to compare clinical outcomes between patients with and without FPE.

Methods: In July 2020, a literature search on FPE (defined as modified Thrombolysis in Cerebral Infarction (TICI) 2c-3 after a single pass) and modified FPE (mFPE, defined as TICI 2b-3 after a single pass) and mechanical thrombectomy for stroke was performed. Using a random-effects meta-analysis, we evaluated the following outcomes for both FPE and mFPE: overall rates, rates by thrombectomy technique, rates of good neurologic outcome (modified Rankin Scale score ≤2 at day 90), mortality, and symptomatic intracerebral hemorrhage (sICH) rate.

Results: Sixty-seven studies comprising 16 870 patients were included. Overall rates of FPE and mFPE were 28% and 45%, respectively. Thrombectomy techniques shared similar FPE (p=0.17) and mFPE (p=0.20) rates. Higher odds of good neurologic outcome were found when we compared FPE with non-FPE (56% vs 41%, OR=1.78) and mFPE with non-mFPE (57% vs 44%, OR=1.73). FPE had a lower mortality rate (17% vs 25%, OR=0.62) than non-FPE. FPE and mFPE were not associated with lower sICH rate compared with non-FPE and non-mFPE (4% vs 18%, OR=0.41 for FPE; 5% vs 7%, OR=0.98 for mFPE).

Conclusions: Our findings suggest that approximately one-third of patients achieve FPE and around half of patients achieve mFPE, with equivalent results throughout thrombectomy techniques. FPE and mFPE are associated with better clinical outcomes.
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http://dx.doi.org/10.1136/neurintsurg-2020-016869DOI Listing
March 2021

Sertoli cell-only syndrome: etiology and clinical management.

J Assist Reprod Genet 2021 Mar 11;38(3):559-572. Epub 2021 Jan 11.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Almost 50% of infertility cases are due to male factors, and spermatogenesis failure is one of the most severe forms of male infertility. Sertoli cell-only syndrome (SCOS) also known as germ cell aplasia is characterized by azoospermia in which the seminiferous tubules of testicular biopsy are lined only with Sertoli cells. The definitive diagnosis of SCOS is by diagnostic testicular biopsy. Although SCOS may be a result of Klinefelter syndrome, most of the SCOS men have a normal karyotype. Along with genetic aberrations, signaling pathways and endocrine processes might be major factors in the development of SCOS. Sperm retrieval and intracytoplasmic sperm injection (ICSI) are available treatments for SCOS. However, some SCOS patients do not have therapeutic options to help them having a biological child. This review aims to summarize our present knowledge about SCOS and to highlight the importance of future researches in the diagnosis and treatment of this disorder.
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http://dx.doi.org/10.1007/s10815-021-02063-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910341PMC
March 2021

High-resolution scanning electron microscopy for the analysis of three-dimensional ultrastructure of clots in acute ischemic stroke.

J Neurointerv Surg 2021 Oct 23;13(10):906-911. Epub 2020 Dec 23.

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

Background: Characterization of acute ischemic stroke (AIS) clots has typically focused on two-dimensional histological analysis of the thrombus. The three-dimensional (3D) architecture and distribution of components within emboli have not been fully investigated. The aim of this study was to examine the composition and microstructure of AIS clots using histology and serial block-face scanning electron microscopy (SBFSEM).

Methods: As part of the multi-institutional STRIP registry, 10 consecutive AIS emboli were collected from 10 patients treated by mechanical thrombectomy. Histological and immunohistochemical analysis was performed to determine clot composition. SBFSEM was used to assess the ultrastructural organization of the clots and specific features of individual components.

Results: Quantification of Martius Scarlett Blue stain identified fibrin (44.4%) and red blood cells (RBCs, 32.6%) as the main components. Immunohistochemistry showed a mean platelet and von Willebrand factor content of 23.9% and 11.8%, respectively. The 3D organization of emboli varied greatly depending on the region analyzed. RBC-rich areas were composed mainly of tightly packed RBCs deformed into polyhedrocytes with scant fibrin fibers interwoven between cells. The regions with mixed composition showed thick fibrin fibers along with platelets, white blood cells and RBC clusters. Fibrin-rich areas contained dense fibrin masses with sparse RBC. In three cases, the fibrin formed a grid-like or a sponge-like pattern, likely due to thrombolytic treatment. Segmentation showed that fibrin fibers were thinner and less densely packed in these cases.

Conclusions: 3D-SEM provides novel and potentially clinically relevant information on clot components and ultrastructure which may help to inform thrombolytic treatment and medical device design.
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http://dx.doi.org/10.1136/neurintsurg-2020-016709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226367PMC
October 2021

Characterizing thrombus with multiple red blood cell compositions by optical coherence tomography attenuation coefficient.

J Biophotonics 2021 03 17;14(3):e202000364. Epub 2020 Dec 17.

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

Embolectomy is one of the emergency procedures performed to remove emboli. Assessing the composition of human blood clots is an important diagnostic factor and could provide guidance for an appropriate treatment strategy for interventional physicians. Immunostaining has been used to identity compositions of clots as a gold-standard procedure, but it is time-consuming and cannot be performed in situ. Here, we proposed that the optical attenuation coefficient of optical coherence tomography (OCT) can be a reliable indicator as a new imaging modality to differentiate clot compositions. Fifteen human blood clots with multiple red blood cell (RBC) compositions from 21% to 95% were prepared using healthy human whole blood. A homogeneous gelatin phantom experiment and numerical simulation based on the Lambert-Beer's law were examined to verify the validity of the attenuation coefficient estimation. The results displayed that optical attenuation coefficients were strongly correlated with RBC compositions. We reported that attenuation coefficients could be a promising biomarker to guide the choice of an appropriate interventional device in a clinical setting and assist in characterizing blood clots.
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http://dx.doi.org/10.1002/jbio.202000364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258800PMC
March 2021

Assessment of Blood Clot Composition by Spectral Optical Coherence Tomography: An In Vitro Study.

Neurointervention 2021 Mar 10;16(1):29-33. Epub 2020 Dec 10.

Neuroradiology Research Laboratory, Department of Radiology, Mayo Clinic, Rochester, MN, USA.

Purpose: Optical coherence tomography (OCT) has the potential for in vivo clot composition characterization in difficult mechanical embolectomy cases. We performed an in vitro study to determine the OCT characteristics of red blood cells (RBCs) and fibrin rich clots.

Materials And Methods: Analogues of 5 compositions of clots (5% to 95% RBCs from Group A to E) were created from human blood. The blood mixture was injected into the bifurcation of a 3D printed bifurcated silicone tube. The OPTISTM Integrated System (St. Jude Medical Inc.) was used to identify the magnitude of OCT signals from different compositions of clots. Martius Scarlett Blue trichrome (MSB) staining was performed to confirm the composition of RBCs and fibrin in each clot.

Results: Group A and B showed less signal attenuation (less than 30%) from its surface to the inside, which indicated high penetration (low-back scattering). Group C indicated intermediate signal attenuation (60%) from its surface to inside the clots, in which signals were found even at the periphery of the clot. Group D and E were superficially signal rich with more signal attenuation (more than 80%) from its surface to the inside indicating low penetration (high-back scattering). Signal-free shadowing was shown in 3 clots in Group E. MSB staining indicated color change (from red in fibrin-rich clots to yellow in RBC-rich clots).

Conclusion: Different compositions of clots can be assessed using OCT. Fibrin-rich clots have homogeneous signals with high penetration, while RBC-rich clots can be recognized as superficially signal rich with low penetration.
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http://dx.doi.org/10.5469/neuroint.2020.00297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946555PMC
March 2021

Characterizing blood clots using acoustic radiation force optical coherence elastography and ultrasound shear wave elastography.

Phys Med Biol 2021 01 26;66(3):035013. Epub 2021 Jan 26.

Department of Radiology, Mayo Clinic, Minnesota, 200 First St SW, Rochester, MN 55905, United States of America. Author to whom any correspondence should be addressed.

Thromboembolism in a cerebral blood vessel is associated with high morbidity and mortality. Mechanical thrombectomy (MT) is one of the emergenc proceduresperformed to remove emboli. However, the interventional approaches such as aspiration catheters or stent retriever are empirically selected. An inappropriate selection of surgical devices can influence the success rate during embolectomy, which can lead to an increase in brain damage. There has been growing interest in the study of clot composition and using a priori knowledge of clot composition to provide guidance for an appropriate treatment strategy for interventional physicians. Developing imaging tools which can allow interventionalists to understand clot composition could affect management and device strategy. In this study, we investigated how clots of different compositions can be characterized by using acoustic radiation force optical coherence elastography (ARF-OCE) and compared with ultrasound shear wave elastography (SWE). Five different clots compositions using human blood were fabricated into cylindrical forms from fibrin-rich (21% red blood cells, RBCs) to RBC-rich (95% RBCs). Using the ARF-OCE and SWE, we characterized the wave velocities measured in the time-domain. In addition, the semi-analytical finite element model was used to explore the relationship between the phase velocities with various frequency ranges and diameters of the clots. The study demonstrated that the wave group velocities generally decrease as RBC content increases in ARF-OCE and SWE. The correlation of the group velocities from the OCE and SWE methods represented a good agreement as RBC composition is larger than 39%. Using the phase velocity dispersion analysis applied to ARF-OCE data, we estimated the shear wave velocities decoupling the effects of the geometry and material properties of the clots. The study demonstrated that the composition of the clots can be characterized by elastographic methods using ARF-OCE and SWE, and OCE demonstrated better ability to discriminate between clots of different RBC compositions, compared to the ultrasound-based approach, especially in clots with low RBC compositions.
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http://dx.doi.org/10.1088/1361-6560/abcb1eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880883PMC
January 2021

Characterization of thrombus composition with multimodality CT-based imaging: an in-vitro study.

J Neurointerv Surg 2021 Aug 28;13(8):738-740. Epub 2020 Oct 28.

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA

Background: CT is the most commonly used imaging modality for acute ischemic stroke evaluation. There is growing interest to use pre-operative imaging to characterize clot composition in stroke. We performed an in-vitro study examining the ability of various CT techniques in differentiation between different clot types.

Methods: Five clot types with varying fibrin and red blood cells (RBCs) densities (5% RBC and 95% fibrin; 25% RBC and 75% fibrin; 50% RBC and 50% fibrin; 75% RBC and 25% fibrin; 95% RBC and 5% fibrin) were prepared and scanned using various CT scanning protocols (single-energy, dual-energy, photon-counting detector CT, mixed images, and virtual monoenergetic images). Martius Scarlett Blue trichrome staining was performed to confirm the composition of each clot. Mean CT values of each type of clot under different scanning protocol were calculated and compared.

Results: Mean CT values of the CT numbers in the five clot specimens for 5%, 25%, and 50% RBC clot were similar across modalities, and increased significantly for 75% and 95% RBC clots (P<0.0001). Mean CT values are highest in the Mono +50 keV images in each type of clot, and they were also significantly higher than all other imaging protocols (P<0.001). Dual-energy CT with Mono +50 keV images showed the greatest difference between attenuation in each type of clot.

Conclusion: Mono +50 keV dual-energy CT scan may be helpful for differentiating between RBC-rich and fibrin-rich thrombi seen in large-vessel occlusion patients.
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http://dx.doi.org/10.1136/neurintsurg-2020-016799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079546PMC
August 2021

Application of platelet-rich plasma (PRP) improves self-renewal of human spermatogonial stem cells in two-dimensional and three-dimensional culture systems.

Acta Histochem 2020 Dec 28;122(8):151627. Epub 2020 Sep 28.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Spermatogonial stem cells (SSCs) are very sensitive to chemotherapy and radiotherapy, so male infertility is a great challenge for prepubertal cancer survivors. Cryoconservation of testicular cells before cancer treatment can preserve SSCs from treatment side effects. Different two-dimensional (2D) and three-dimensional (3D) culture systems of SSCs have been used in many species as a useful technique to in vitro spermatogenesis. We evaluated the proliferation of SSCs in 2D and 3D culture systems of platelet-rich plasma (PRP). testicular cells of four brain-dead patients cultivated in 2D pre-culture system, characterization of SSCs performed by RT-PCR, flow cytometry, immunocytochemistry and their functionality assessed by xenotransplantation to azoospermia mice. PRP prepared and dosimetry carried out to determine the optimized dose of PRP. After preparation of PRP scaffold, cytotoxic and histological evaluation performed and SSCs cultivated into three groups: control, 2D culture by optimized dose of PRP and PRP scaffold. The diameter and number of colonies measured and relative expression of GFRa1 and c-KIT evaluated by real-time PCR. Results indicated the expression of PLZF, VASA, OCT4, GFRa1 and vimentin in colonies after 2D pre-culture, xenotransplantation demonstrated proliferated SSCs have proper functionality to homing in mouse testes. The relative expression of c-KIT showed a significant increase as compared to the control group (*: p < 0.05) in PRP- 2D group, expression of GFRa1 and c-KIT in PRP scaffold group revealed a significant increase as compared to other groups (***: p < 0.001). The number and diameter of colonies in the PRP-2D group showed a considerable increase (p < 0.01) as compared to the control group. In PRP- scaffold group, a significant increase (p < 0.01) was seen only in the number of colonies related to the control group. Our results suggested that PRP scaffold can reconstruct a suitable structure to the in vitro proliferation of SSCs.
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http://dx.doi.org/10.1016/j.acthis.2020.151627DOI Listing
December 2020

Isolation, identification and differentiation of human spermatogonial cells on three-dimensional decellularized sheep testis.

Acta Histochem 2020 Dec 23;122(8):151623. Epub 2020 Sep 23.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Improvement of in vitro culture methods of Spermatogonial Stem Cells (SSCs) is known to be an effective procedure for further study of the process of spermatogenesis and can offer effective therapeutic modality for male infertility. Tissue decellularization by providing natural 3D and extracellular matrix (ECM) conditions for cell growth can be an alternative procedure to enhance in vitro culture conditions. In the present study, the testicular tissues were taken from brain death donors. After enzymatic digestion, the tissue cells were isolated and cultured for four weeks. Then the identity of the SSCs was confirmed using anti-GFRα1 and anti-PLZF antibodies via immunocytochemistry (ICC). The differentiation capacity of SSCs were evaluated by culture of them on a layer of decellularized testicular matrix (DTM) prepared from sheep testis, as well as under two-dimensional (2D) culture with differentiation medium. After four and six weeks of the initiation of differentiation culture, the pre-meiotic, meiotic and post- meiotic genes at the mRNA and protein levels was examined via qPCR and ICC methods, respectively. The results showed that pre-meiotic, meiotic and post-meiotic genes expressions were significantly higher in the cells cultured in DTM substrate (P ≤ 0.01).The present study indicated that, the natural structure of ECM prepare the suitable conditions for further study of the spermatogenesis process in the in vitro and contributes to the maintenance and treatment of male infertility.
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http://dx.doi.org/10.1016/j.acthis.2020.151623DOI Listing
December 2020

Three-dimensional co-culture of human spermatogonial stem cells with Sertoli cells in soft agar culture system supplemented by growth factors and Laminin.

Acta Histochem 2020 Jul 13;122(5):151572. Epub 2020 Jun 13.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Application of a three-dimensional (3D) culture system for in vitro proliferation and differentiation of human spermatogonial stem cells (SSCs) is a useful tool for the investigation of the spermatogenesis process and the management of male infertility particularly in prepubertal cancer patients. The main purpose of this study was to investigate the proliferation of human SSCs co-cultured with Sertoli cells in soft agar culture system (SACS) supplemented by Laminin and growth factors. Testicular cells were isolated from testes of brain-dead patients and cultured in two-dimensional (2D) culture system for 3 weeks. After 3 weeks, functional SSCs were evaluated by xenotransplantation and also identification of cells was assessed by immunocytochemistry, flow cytometry, and RT-PCR. Then, SSCs and Sertoli cells were transferred to the upper layer of SACS for 3 weeks. After 3 weeks, the number of colonies and the expression of specific SSCs and Sertoli cell markers, as well as apoptotic genes were evaluated. Our results showed that transplanted SSCs, migrated into the basement membrane of seminiferous tubules of recipient mice. The expression of PLZF, α6-Integrin, and Vimentin proteins in SSCs and Sertoli cells were observed in 2D and 3D culture systems. The expression rate of PLZF, α6-Integrin, Bcl2, and colony number in SACS supplemented by Laminin and growth factors group were significantly higher than non-supplemented groups (P ≤ 0.01), but the expression rate of c-kit and Bax in supplemented group were significantly lower than non-supplemented groups (P ≤ 0.05). This 3D co-culture system decreased apoptosis and increased propagation of human SSCs. Therefore, this designed system can be utilized to increase the proliferation of human SSCs in prepubertal male cancer and azoospermic men to obtain an adequate SSCs number to outotransplant success and in vitro spermatogenesis.
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http://dx.doi.org/10.1016/j.acthis.2020.151572DOI Listing
July 2020

MicroRNAs signatures, bioinformatics analysis of miRNAs, miRNA mimics and antagonists, and miRNA therapeutics in osteosarcoma.

Cancer Cell Int 2020 17;20:254. Epub 2020 Jun 17.

Department of Information Sciences, Tehran University of Medical Sciences, Tehran, Iran.

MicroRNAs (miRNAs) involved in key signaling pathways and aggressive phenotypes of osteosarcoma (OS) was discussed, including PI3K/AKT/MTOR, MTOR AND RAF-1 signaling, tumor suppressor P53- linked miRNAs, NOTCH- related miRNAs, miRNA -15/16 cluster, apoptosis related miRNAs, invasion-metastasis-related miRNAs, and 14Q32-associated miRNAs cluster. Herrin, we discussed insights into the targeted therapies including miRNAs (i.e., tumor-suppressive miRNAs and oncomiRNAs). Using bioinformatics tools, the interaction network of all OS-associated miRNAs and their targets was also depicted.
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http://dx.doi.org/10.1186/s12935-020-01342-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302353PMC
June 2020

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

J Neurointerv Surg 2021 Jan 2;13(1):91-95. Epub 2020 Jun 2.

Neurological Surgery, Tulane Medical Center Downtown, New Orleans, Louisiana, USA.

Background: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion.

Methods: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches.

Results: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035).

Conclusion: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.
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http://dx.doi.org/10.1136/neurintsurg-2020-015992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708402PMC
January 2021

Calcium silicate cement interface with restorative materials through layering after different time intervals.

Odontology 2021 Jan 27;109(1):210-221. Epub 2020 Apr 27.

Division of Dental Biomaterials, Center for Dental and Oral Medicine, Clinic for Reconstructive Dentistry, University of Zürich, Zürich, Switzerland.

The aim was to evaluate the interfacial characteristics of Biodentine, CEM Cement, and ProRoot MTA when restored with different final restorative materials after different time intervals. Biodentine, CEM Cement and ProRoot MTA were layered with amalgam, composite resin or light cure glass ionomer cement. Layering was done either immediately, 24 or 72 h after cement placement. The interface of cements with restorative materials was characterized using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) after separation. Vickers surface microhardness test was also performed on the interface. Statistical analysis included two-way Anova, Dunnett T3, and Tukey HSD. The significance level was set at P < 0.05. The highest microhardness values were seen when restorative materials were layered after 24 h in the case of Biodentine, and after 72 h in the case of CEM Cement and ProRoot MTA. In ProRoot MTA no significant difference was seen in the microhardness when layered with different restorative materials regardless of the time of layering. In immediate layering, Biodentine exhibited the highest microhardness values. Both immediate and delayed layering resulted in element transfer between calcium silicate cements (CSCs) and restorative materials. Deposition and depletion of element occurs subsequent to layering of restorative materials on CSCs. When immediate layering is necessary, Biodentine may be a better option compared to other CSCs evaluated.
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http://dx.doi.org/10.1007/s10266-020-00521-zDOI Listing
January 2021

Basal characterization and in vitro differentiation of putative stem cells derived from the adult mouse ovary.

In Vitro Cell Dev Biol Anim 2020 Jan 3;56(1):59-66. Epub 2020 Jan 3.

Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Colorado-Denver, Denver, CO, USA.

Lately, stem cell approaches have provided new information on reproductive organ function and additionally recommended novel treatment possibilities. The type(s) and differentiation potential of stem cells present in the mammalian ovary are largely unknown; while oogonial stem cells have been reported, we explored the possibility that multipotent stem cells may reside in the ovary and have wide differentiation potential. In this experimental study, homogenates of whole mouse ovaries were sorted using the stem cell surface markers stem cell antigen-1 and stage specific embryonic antigen-1/CD15. Viable double-positive cells 3-10 μm in diameter were evaluated immediately after sorting and after culture using differentiation conditions. Ovarian-derived stem cells were differentiated into the three main cell types: adipocytes, chondrocytes, or osteocytes. The subsequent culture was performed in media containing bone morphogenetic protein 4 (BMP-4) and/or retinoic acid (RA). RA, BMP-4 or the two agents in combination, consistently stimulated germ cell gene expression. RA treatment strongly stimulated germline gene expression and also the development of cells that were morphologically reminiscent of oocytes. The germ cell genes Dazl, Ddx4, Figla, Gdf-9, Nobox, Prdm9, and Sycp-1 were all detected at low levels. Remarkably, treatment with BMP-4 alone significantly increased protein expression of the granulosa cell product anti-Müllerian hormone (AMH). We have shown that an inclusive isolation protocol results in the consistent derivation of multipotent stem cells from the adult ovary; these cells can be differentiated towards the germ cell fate (RA alone), somatic ovarian cell fate as indicated by AMH production (BMP-4 alone), or classical mesenchymal cell types. Taken together, these data suggest the presence of multipotent mesenchymal stem cells in the murine ovary.
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http://dx.doi.org/10.1007/s11626-019-00411-xDOI Listing
January 2020

In Vitro Spermatogenesis by Three-dimensional Culture of Spermatogonial Stem Cells on Decellularized Testicular Matrix.

Galen Med J 2019 15;8:e1565. Epub 2019 Dec 15.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: In the males, Spermatogonial Stem Cells (SSCs) contribute to the production of sex cells and fertility. SSCs culture can operate as an effective strategy for studies on spermatogenesis and male infertility treatment. Cell culture in a three-dimensional (3D) substrate, relative to a two-dimensional substrate (2D), creates better conditions for cell interaction and is closer to conditions. In the present study, in order to create a 3D matrix substrate, decellularized testicular matrix (DTM) was used to engender optimal conditions for SSCs culture and differentiation.

Materials And Methods: After, testicular cells enzymatic extraction from testes of brain-dead donors, the SSCs were proliferated in a specific culture medium for four weeks, and after confirming the identity of the colonies derived from the growth of these cells, they were cultured on a layer of DTM as well as in 2D condition with a differentiated culture medium. In the Sixth week since the initiation of the differentiation culture, the expression of pre meiotic ( ), meiotic () and post meiotic () genes were measured in both groups.

Results: The results indicated that the expression of pre meiotic, meiotic and post meiotic genes was significantly higher in the cells cultured on DTM (P ≤ 0.001).

Conclusion: SSCs culture in DTM with the creation of ECM and similar conditions with in vivo can be regarded as a way of demonstrating spermatogenesis in vitro, which can be adopted as a treatment modality for male infertility.
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http://dx.doi.org/10.31661/gmj.v8i0.1565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344169PMC
December 2019

Evaluation of Enkephalin-Degrading Enzymes in Sperm from Heroin-Addicted Men.

Int J Fertil Steril 2020 Jan 11;13(4):301-306. Epub 2019 Nov 11.

Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: The aim of this study was to investigate two enkephalin-degrading enzymes, aminopeptidase N (APN/ CD13) and endopeptidase (NEP/CD10), gene and protein expression levels in sperm samples of fertile and heroinaddicted men, and the correlation between their expressions and semen quality.

Materials And Methods: In this case-controlled study, semen was collected from 24 normozoospermic healthy (as a control group) and 24 heroin-addicted men donors (as case or addiction group). Sperm cells isolated by Cook Medical gradient (40-80%) and followed up by swim-up techniques were used for real-time quantitative polymerase chain reaction (qPCR) and flow cytometry techniques to assess and genes and proteins subsequently. Semen parameters were analyzed by computer-assisted sperm analysis.

Results: The findings revealed that there were significant differences in sperm total motility (41.07 ± 3.63 vs. 63.03 ± 3.31 %, P=0.0001), progressive motility (35.21 ± 2.64 vs. 20.93 ± 3.22%, P=0.001) and viability (69.9 ± 4.69 vs. 86.81 ± 1.26 %, P=0.002) in the addicted group vs. control ones. and gene expression levels in the addicted group decreased compared with the control ones (1.00 ± 0.67 vs. 0.36 ± 0.13, P= 0.008 and 1.07 ± 0.11 vs. 0.52 ± 0.12 0.002, respectively). Flow cytometry analysis showed that the average percent of APN/CD13 in heroin consumers significantly decreased compared with the healthy ones, while NEP/CD10 rate between two groups was similar. We also observed that duration of drug dependence is correlated with sperm viability (r=-0.627, P=0.016) and motility (r=-0.410, P=0.05), (r=-0.434, P= 0.049), and (r=-0.641, P=0.002) gene expression levels.

Conclusion: We conclude that semen quality and enkephalin-degrading enzymes were altered in heroin-addicted men. other confirming the internal validity of our estimates.
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http://dx.doi.org/10.22074/ijfs.2020.5817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875862PMC
January 2020

Human Menstrual Blood Stem Cell-Derived Granulosa Cells Participate in Ovarian Follicle Formation in a Rat Model of Premature Ovarian Failure .

Cell Reprogram 2019 10;21(5):249-259

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

We recently reported the application of human menstrual blood stem cells' (HuMenSCs) transplantation as a treatment modality in a rat model of premature ovarian failure (POF). We continued to investigate further in this respect. Female rats were injected intraperitoneally with 36 mg/kg busulfan. HuMenSCs were obtained, grown, and analyzed for immunophenotypic features at passage three. The cells were labeled with CM-Dil and infused into the rats. There were four groups: normal, negative control, treatment, and Sham. One month after treatment, the ovaries were collected and weighed. Histological sections were prepared from the ovary and HuMenSCs were tracking. Subsequently, we examined the changes of expression of Bax and B cell lymphoma 2 (Bcl2) genes by real-time polymerase chain reaction assay. One month after HuMenSCs transplantation, these cells were located in the ovarian interstitium and granulosa cells (GCs). The number of TUNEL-positive cells significantly decreased in the treatment group. Also the expression level of Bax genes, unlike Bcl2 gene, significantly decreased compared with negative and sham groups. In our study, HuMenSCs were tracked in ovarian tissues within 2 months after transplantation, and they differentiated into GCs. Therefore, the use of these cells can be a practical and low-cost method for the treatment of POF patients.
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http://dx.doi.org/10.1089/cell.2019.0020DOI Listing
October 2019
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