scholarly journals Effect of local and systemic inflammation on gingival mesenchymal stem cells

2018 ◽  
Vol 8 (2) ◽  
pp. 60-66
Author(s):  
Ting Jing Kweh ◽  
Ru Yueh Tham ◽  
Jian Yee Gu ◽  
Ahsan Md Shahidul ◽  
Pulikkotil Shaju Jacob ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Systemic Inflammation ◽  
Type Ii Diabetes Mellitus ◽  
Low Grade ◽  
Tissue Samples ◽  
Inflammatory Status ◽  
Hematoxylin And Eosin ◽  
Group 2 ◽  
Group 1

Background. The present study was undertaken to determine the effect of local and systemic inflammation on the quantity and localization of gingival mesenchymal stem cells (gMSCs). Methods. Gingival samples were collected from 34 systemically healthy (group 1) and 10 consenting adult patients with type II diabetes mellitus (T2DM) (group 2), who had reported for various dental treatments, requiring excision of gingival tissues as part thereof. The tissue samples were further stratified into three categories: healthy gingiva, gingivitis-affected and periodontitis-affected. Samples mounted on slides were stained with hematoxylin and eosin (H&amp;amp;E) while CD105 antibody was used for immunohistochemistry staining. Immuno-positive cells were identified as gMSCs. Three gMSCpopulated areas in each sample were selected to determine the density of gMSCs. Results. The density of gMSCs was significantly higher (P<0.05) in sections of gingival tissues affected by gingivitis and periodontitis compared to those of normal gingiva. However, there were no significant differences in the densities of gMSCs in tissues of patients with T2DM and those of healthy subjects. Conclusion. Local inflammatory status appeared to increase the density of gMSCs. In the presence of periodontitis, an added low-grade systemic inflammation (T2DM) did not appear to affect the density of gMSCs.

scholarly journals Umbilical Cord Blood Mesenchymal Stem Cells as an Infertility Treatment for Chemotherapy Induced Premature Ovarian Insufficiency

Biomedicines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 7 ◽  
Author(s):  
Sara Mohamed ◽  
Shahinaz Shalaby ◽  
Soumia Brakta ◽  
Lelyand Elam ◽  
Amro Elsharoud ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Serum Levels ◽  
Ovarian Insufficiency ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. Materials and Method: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions. The second was to prove improved fertility. A total of 36 mice were randomly assigned; 6 mice into each of 3 groups for two experiments. Group 1 (control), group 2 (sham chemotherapy), group 3 (stem cells). Results: In the first experiment, post-UCMSCs treatment (group 3) showed signs of restored ovarian function in the form of increased ovarian weight and estrogen-dependent organs (liver, uterus), increased follicular number, and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 versus group 2. Immuno-histochemistry analysis demonstrated a higher expression of AMH, follicle stimulating hormone receptor (FSHR) and Inhibin A in the growing follicles of group 3 versus group 2. In the second experiment, post-UCMSCs treatment (group 3) pregnancy rates were higher than group 2, however, they were still lower than group 1. Conclusion: We demonstrated the ability of UCMSCs to restore fertility in female cancer survivors with POI and as another source of stem cells with therapeutic potentials.

scholarly journals Synergic Effect of Combined Therapy of Hyperbaric Oxygen and Adipose-derived Mesenchymal Stem Cells on Improving Neurological Function After Acute Traumatic Spinal Cord Injury in Rat

2021 ◽  
Author(s):  
Tsung-Cheng Yin ◽  
Pei-Lin Shao ◽  
Kuan-Hung Chen ◽  
Kun-Chen Lin ◽  
John Y. Chiang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Traumatic Spinal Cord Injury ◽  
Voltage Gated ◽  
Cord Injury ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

Abstract Background: This study tested whether combined hyperbaric oxygen (HBO) and allogenic adipose-derived mesenchymal stem cells (ADMSCs) would be superior to either one for improving the neurological function in rat after acute traumatic spinal cord injury (TSCI) in rat. Methods and Results: Adult-male SD rats (n=40) were equally categorized into group 1 (sham-operated control), group 2 (TSCI), group 3 (TSCI + HBO for 1.5h/day for 14 consecutive days after TSCI), group 4 (TSCI + ADMSCs/1.2x106 cells by intravenous injection at 3h and days 1/2 after TSCI) and group 5 (TSCI + HBO + ADMSCs), euthanized and spinal-cord tissue was harvested by day 49 after TSCI. The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2), inflammatory-signaling (TLR-4/MyD88/IL-1ß/TNF-α/substance-p), cell-stress signaling (PI3K/p-AKT/p-mTOR) and the voltage gated sodium channel (Nav1.3/1.8/1.9) biomarkers were highest in group 2, lowest in group 1 and significantly lower in group 5 than in groups 3/4 (all p<0.0001), but they did not differ between groups 3/4. The spinal cord-damaged area, the cellular levels of inflammatory/DNA-damaged (CD68+/GFAP+/γ-H2AX+ cells), MAPK family biomarkers (p-P38/p-JNK/p-ERK1/2) and cellular expressions of voltage gated sodium channel (Nav.1.3, Nav.1.8 and Nav.1.9 in NF200+ cells) as well as the pain facilitated cellular expressions (p-P38+/peripherin+ cells, p-JNK+/peripherin+ cells, p-ERK/NF200+ cells) exhibited an identical pattern of inflammation, whereas the neurological integrity displayed an opposite pattern of inflammation among the groups (all p<0.0001). Conclusion: Combined HBO-ADMSCs therapy offered additional benefits for protecting the neurological architectural and functional integrity against acute TSCI.

scholarly journals Combined Therapy with Extracorporeal Shock Wave and Adipose-Derived Mesenchymal Stem Cells Remarkably Improved Acute Ischemia-Reperfusion Injury of Quadriceps Muscle

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Tsung-Cheng Yin ◽  
Re-Wen Wu ◽  
Jiunn-Jye Sheu ◽  
Pei-Hsun Sung ◽  
Kuan-Hung Chen ◽  
...  
Keyword(s):  
Shock Wave ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion ◽  
Quadriceps Muscle ◽  
Control Group ◽  
Opposite Pattern ◽  
Extracorporeal Shock Wave ◽  
Group 2 ◽  
Group 1

Extracorporeal shock wave (ECSW) and adipose-derived mesenchymal stem cells (ADMSCs) have been recognized to have capacities of anti-inflammation and angiogenesis. We tested the hypothesis that ECSW and ADMSC therapy could attenuate ischemia-reperfusion- (IR-) induced thigh injury (femoral artery tightened for 6 h then the tightness was relieved) in rats. Adult male SD rats (n=30) were divided into group 1 (sham-control), group 2 (IR), group 3 (IR + ECSW/120 impulses at 0.12 mJ/mm2 given at 3 h/24 h/72 h after IR), group 4 (allogenic ADMSC/1.2 × 106 cell intramuscular and 1.2 × 106 cell intravenous injections 3 h after IR procedure), and group 5 (ECSW + ADMSC). At day 7 after the IR procedure, the left quadriceps muscle was harvested for studies. At 18 h after the IR procedure, serum myoglobin/creatine phosphokinase (CPK) levels were highest in group 2, lowest in group 1, and with intermediate values significantly progressively reduced in groups 3 to 5 (all p<0.0001). By day 5 after IR, the mechanical paw-withdrawal threshold displayed an opposite pattern of CPK (all p<0.0001). The protein expressions of inflammatory, oxidative-stress, apoptotic, fibrotic, DNA-damaged, and mitochondrial-damaged biomarkers and cellular expressions of inflammatory and DNA-damaged biomarkers exhibited an identical pattern of CPK among the five groups (all p<0.0001). The microscopic findings of endothelial-cell biomarkers and number of arterioles expressed an opposite pattern of CPK, and the angiogenesis marker was significantly progressively increased from groups 1 to 5, whereas the histopathology showed that muscle-damaged/fibrosis/collagen-deposition areas exhibited an identical pattern of CPK among the five groups (all p<0.0001). In conclusion, ECSW-ADMSC therapy is superior to either one applied individually for protecting against IR-induced thigh injury.

scholarly journals Differentiation of bone marrow derived mesenchymal stem cells into male germ-like cells in co-culture with testicular cells

2019 ◽  
Vol 53 (2) ◽  
pp. 93-99
Author(s):  
Nasim Malekmohamadi ◽  
Alireza Abdanipour ◽  
Mehrdad Ghorbanlou ◽  
Saeed Shokri ◽  
Reza Shirazi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Mouse Bone Marrow ◽  
Testicular Cells ◽  
Morphogenetic Protein ◽  
Group 2 ◽  
Group 1

AbstractObjective. Stem cell therapy, specifically, pre-induction of mesenchymal stem cells toward male germ-like cells may be useful in patients with azoospermia. The aim of this study was to evaluate in vitro differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into male germ-like cells by indirect co-culture with testicular cells in the presence of bone morphogenetic protein 4 (BMP4).Methods. Experimental groups included: control (mouse BMSCs), treatment group-1 (BMSCs treated with BMP4), treatment group-2 (indirect co-culture of BMSCs with mouse testicular cells in the presence of BMP4) and treatment group-3 (indirect co-culture of BMSCs with testicular cells). BMSCs-derived male germ-like cells were evaluated by the expression of Dazl, and Stra8 using RT-qPCR.Results. Stra8 gene expression was significantly increased in the treatment group-2 and Dazl gene was significantly increased in the treatment group-1 compared to other groups. In conclusion, indirect co-culturing of BMSCs with testicular cells and BMP4 leads to the differentiation of BMSCs into male germ-like cells which express specific male germ-like genes. Testicular cells released factors that contributed to the differentiation of BMSCs into male germ progenitor cells.Conclusion. This study suggests that mesenchymal stem cells may be differentiated into male germ-like cells and therefore, may be a novel treatment option for men with azoospermia.

scholarly journals Assessment of the Role of NOGO Gene Block in Enhancing the Neuro-regenerative Effect of Mesenchymal Stem Cells.

2021 ◽  
Author(s):  
Eman Youssef ◽  
Hala Gabr ◽  
Nirmeen A Kishk ◽  
Maha Baligh Zickri ◽  
Shahira KA Botros ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Glial Cells ◽  
Therapeutic Potential ◽  
P Value ◽  
P Values ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal disease. Mesenchymal stem cells (MSCs) have a therapeutic potential in neuronal diseases, factors as NOGO-A limit axonal regeneration. In this study, gene silencing was used to suppress Nogo-A expression in MSCs to enhance its neuro-regenerative role. Methods: mouse models of motor neuron degeneration were created, effect of non-modified and plasmid transfected MSCs were studied clinically and histologically. Group 1 received no treatment. Group 2 received IV injection of non modified MSCs and sacrificed after 8 days (subgroup 2a) and 15 days (subgroup 2b) following treatment, Group 3 received IV injection of transfected MSCs and were sacrificed after 8 days (subgroup 3a) and 15 days (subgroup 3b) following treatment. Results: A significant increase in weight and motor scores of subgroups 2a & 2b occurred in comparison to subgroups1a & 1b respectively (p values <0.001, <0.001, 0.001 & 0.026 respectively), GAP43 expression in group 2 mice was significantly higher compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in group 2 were significantly lower compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in subgroup 2b were significantly less in comparison to subgroup 2a (p values = 0.002 and 0.03) indicating an improvement with time. GAP43 in subgroup 2b was significantly higher compared to subgroup 2a (p value = 0.030).Weight and motor power in group 3 mice was significantly higher when compared to group 1 on days; 14 and 21 (p values <0.001, <0.001, <0.001 and 0.008) respectively. Deformed neurons and glial cells in group 3 mice were significantly lower when compared to group 1 mice (p values <0.001). GAP43 expression in group 3 mice was significantly higher when compared to group1 (p value <0.001). Deformed neurons in subgroup 3b was significantly less than subgroup 3a (p value <0.001). GAP43 expression in group 3 mice was significantly increased when compared to group 2 mice (p value <0.001).Conclusion: NOGO-A gene SiRNA is a potential enhancer of the neuro-regenerative action of MSCs.

scholarly journals Management of toxic optic neuropathy via a combination of Wharton’s jelly-derived mesenchymal stem cells with electromagnetic stimulation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Emin Özmert ◽  
Umut Arslan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Optic Neuropathy ◽  
Electromagnetic Stimulation ◽  
Toxic Optic Neuropathy ◽  
Delta Change ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Abstract Purpose To investigate the effect of the combination of Wharton's jelly derived mesenchymal stem cells (WJ-MSC) and high frequency repetitive electromagnetic stimulation (rEMS) in the therapy of toxic optic neuropathies with severe symptoms after the available current therapy modalities which were unsucessful. Material and methods This prospective, open-label clinical phase-3 study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology between April 2019 and April 2021. Thirty-six eyes of 18 patients with toxic optic neuropathy (TON) were included in the study. Within 1–3 months after the emergency interventions, patients with various degrees of sequela visual disturbances were studied in this clinical trial. The cases were divided into three groups according to similar demographic characteristics. Group 1: Consists of 12 eyes of 12 patients treated with the WJ-MSC and rEMS combination in one eye. Group 2: Consists of 12 eyes of 12 patients treated with only rEMS in one eye. Group 3: Consists of 12 eyes of six patients treated with only WJ-MSC in both eyes. The course was evaluated by comparing the quantitive functional and structural assessment parameters measured before and at the fourth month of applications in each group. Results The mean best corrected visual acuity (BCVA) delta change percentages of the groups can be ranked as: Group 1 (47%) > Group 3 (32%) > Group 2 (21%). The mean fundus perimetry deviation index (FPDI) delta change percentages of the groups can be ranked as: Group 1 (95%) > Group 2 (33%) > Group 3 (27%). The mean ganglion cell complex (GCC) thickness delta change (decrease in thickness) percentages can be ranked as: Group 1 (− 21%) > Group 3 (− 15%) > Group 2 (− 13%). The visual evoked potential (VEP) P100 latency delta change percentages of the groups can be ranked as: Group 1 (− 18%) > Group 3 (− 10%) > Group 2 (− 8%). The P100 amplitude delta change percentages of the groups can be ranked as: Group 1 (105%) > Group 3 (83%) > Group 2 (24%). Conclusion Toxic optic neuropathies are emergent pathologies that can result in acute and permanent blindness. After poisoning with toxic substances, progressive apoptosis continues in optic nerve axons and ganglion cells. After the proper first systemic intervention in intensive care clinic, the WJ-MSC and rEMS combination seems very effective in the short-term period in cases with TON. To prevent permanent blindness, a combination of WJ-MSC and rEMS application as soon as possible may increase the chance of success in currently untreatable cases. Trial Registration ClinicalTrials.gov ID: NCT04877067.

scholarly journals Adipose-derived Mesenchymal Stem Cells Improve the Healing of Tracheoesophageal Fistula in a Beagle Model 

2021 ◽  
Author(s):  
Yuchao Wang ◽  
Shifang Yang ◽  
Pingping Chen ◽  
Hanyi Xu ◽  
Jinghua Cui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tracheoesophageal Fistula ◽  
Saline Water ◽  
Clinical Problem ◽  
Endoscopic Observation ◽  
Volume Group ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Tracheoesophageal fistula (TEF) is still a devastating clinical problem with high mortality. New clinical strategies were developed to sustain survival time. Mesenchymal stem cells were applied in many clinical wound healing fields. This study aims to investigate the main effect of stem cell to TEF.Material and Method We established a beagle model with TEF by punching the trachea and esophagus membrane and suturing. The beagles were divided into three groups (group 1 = 1, group 2 = 6, group 3 = 6). Group 2 and 3 received a TEF building operation. Group 3 were injected 2 ml stem cells (106 per animal), and group 2 injected saline water with same volume. Group 1 did not receive any intervention. All animals receipted total parental nutrition. The closure degree of fistula tissue was observed by bronchoscope and post-mortem after 35 d.Result Morphologic and histopathologic changes of fistulas were assessed by gross and endoscopic observation. The fistulas diameter was measured. In 35 d postoperatively, group 2 showed that 3 animals died for acute smother, 2 animal died for severe chronic pneumonia and 1 animal with consistent fistula. Group 3 showed that 2 animals fully closed, 3 animals fistula diameter significantly decreased, and 1 animal died for acute smother. In autopsy result, group 2 animals showed severer pneumonia degree than group 3 animals in 35 d.Conclusion The transplantation of stem cells can promote healing degree of TEF without any complications and relieve pneumonia at the same time.

scholarly journals Protective/restorative role of the adipose tissue-derived mesenchymal stem cells on the radioiodine-induced salivary gland damage in rats

2017 ◽  
Vol 51 (3) ◽  
pp. 307-316 ◽  
Author(s):  
Güleser Saylam ◽  
Ömer Bayır ◽  
Salih Sinan Gültekin ◽  
Ferda Alparslan Pınarlı ◽  
Ünsal Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Salivary Gland ◽  
Study Groups ◽  
Significant Deterioration ◽  
Group 6 ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

AbstractBackgroundTo analyze protective/regenerative effects of adipose tissue-derived mesenchymal stem cells (ADMSC) on131I-Radioiodine (RAI)-induced salivary gland damage in rats.Materials and MethodsStudy population consisted of controls (n:6) and study groups (n:54): RAI (Group 1), ADMSC (Group 2), amifostine (Group 3), RAI+amifostine (Group 4), concomitant RAI+ADMSC (Group 5) and RAI+ADMSC after 48 h (Group 6). We used light microscopy (LM), transmission electron microscopy (TEM), and salivary gland scintigraphy (SGS), and analyzed data statistically.ResultsWe observed the homing of ADMSC in salivary glands at 1stmonth on LM. RAI exposure affected necrosis, periductal fibrosis, periductal sclerosis, vascular sclerosis and the total sum score were in a statistically significant manner (P< 0.05). Intragroup comparisons with LM at 1stand 6thmonths revealed statistically significant improvements in Group 6 (P< 0.05) but not in Groups 4 and 5. Intergroup comparisons of the total score showed that Groups 4 and 5 in 1stmonth and Group 6 in 6thmonth had the lowest values. TEM showed vacuolization, edema, and fibrosis at 1stmonth, and an improvement in damage in 6thmonth in Groups 5 and 6. SGSs revealed significant differences for the maximum secretion ratio (Smax) (P= 0.01) and the gland-to-background ratio at a maximum count (G/BGmax) (P= 0. 01) at 1stmonth, for G/BGmax (P= 0.01), Smax (P= 0.01) and the time to reach the maximum count ratio over the time to reach the minimum count (Tmax/Tmin) (P= 0.03) at 6thmonth. 1stand 6thmonth scans showed differences for Smax and G/BGmax (P= 0.04), but not for Tmax/Tmin (p> 0.05). We observed a significant deterioration in gland function in group 1, whereas, mild to moderate deteriorations were seen in protective treatment groups.ConclusionsOur results indicated that ADMSC might play a promising role as a protective/regenerative agent against RAI-induced salivary gland dysfunction.

scholarly journals Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yen-Ta Chen ◽  
Fei-Chi Chuang ◽  
Chih-Chao Yang ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Testicular Torsion ◽  
Ischemia Reperfusion ◽  
Opposite Pattern ◽  
Protein Expressions ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

Abstract Background This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. Methods and results Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001). Conclusion Mel-ADMSCs effectively protected the testis against TTIR injury.

Extending the multistage surgical strategy for recurrent initially low-grade gliomas: functional and oncological outcomes in 31 consecutive patients who underwent a third resection under awake mapping

2021 ◽  
pp. 1-10 ◽  
Author(s):  
Noor Hamdan ◽  
Hugues Duffau
Keyword(s):  
High Rate ◽  
Karnofsky Performance Scale ◽  
Consecutive Series ◽  
Low Grade ◽  
Oncological Treatment ◽  
The Third ◽  
Oncological Outcomes ◽  
Group 2 ◽  
Group 1

OBJECTIVE Maximal safe resection is the first treatment in diffuse low-grade glioma (DLGG). Due to frequent tumor recurrence, a second surgery has already been reported, with favorable results. This study assesses the feasibility and functional and oncological outcomes of a third surgery in recurrent DLGG. METHODS Patients with DLGG who underwent a third functional-based resection using awake mapping were consecutively selected. They were classified into group 1 in cases of slow tumor regrowth or group 2 if a radiological enhancement occurred during follow-up. All data regarding clinicoradiological features, histomolecular results, oncological treatment, and survival were collected. RESULTS Thirty-one patients were included, with a median age of 32 years. There were 20 astrocytomas and 11 oligodendrogliomas in these patients. Twenty-one patients had medical oncological treatment before the third surgery, consisting of chemotherapy in 19 cases and radiotherapy in 8 cases. No neurological deficit persisted after the third resection except mild missing words in 1 patient, with 84.6% of the patients returning to work. The median follow-up duration was 13.1 ± 3.4 years since diagnosis, and 3.1 ± 2.9 years since the third surgery. The survival rates at 7 and 10 years were 100% and 89.7%, respectively, with an estimated median overall survival of 17.8 years since diagnosis. A comparison between the groups showed that the Karnofsky Performance Scale score dropped below 80 earlier in group 2 (14.3 vs 17.1 years, p = 0.01). Median residual tumor volume at the third surgery was smaller (2.8 vs 14.4 cm3, p = 0.003) with a greater extent of resection (89% vs 70%, p = 0.003) in group 1. CONCLUSIONS This is the first consecutive series showing evidence that, in select patients with progressive DLGG, a third functional-based surgery can be achieved using awake mapping with low neurological risk and a high rate of total resection, especially when reoperation is performed before malignant transformation.

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