Angiogenic Potential of Various Oral Cavity-Derived Mesenchymal Stem Cells and Cell-Derived Secretome: A Systematic Review and Meta-Analysis.

Recent evidence suggests the immense potential of human mesenchymal stem cell (hMSC) secretome conditioned medium-mediated augmentation of angiogenesis. However, angiogenesis potential varies from source and origin. The hMSCs derived from the oral cavity share an exceptional quality due to their origin from a hypoxic environment. Our systematic review aimed to compare the mesenchymal stem cells (MSCs) derived from various oral cavity sources and cell-derived secretomes, and evaluate their angiogenic potential. A literature search was conducted using PubMed and Scopus from January 2000 to September 2020. Source-wise outcomes were systematically analyzed using in vitro, in vivo, and in ovo studies, emphasizing endothelial cell migration, tube formation, and blood vessel formation. Ninety-four studies were included in the systematic review, out of which 4 studies were subsequently included in the meta-analysis. Prominent growth factors and other bioactive components implicated in improving angiogenesis were included in the respective studies. The findings suggest that oral tissues are a rich source of hMSCs. The meta-analysis revealed a positive correlation between dental pulp-derived MSCs (DPMSCs) and stem cells derived from apical papilla (SCAP) compared to human umbilical cord-derived endothelial cell lines as a control. It shows a statistically significant positive correlation between the co-culture of human umbilical vein endothelial cells (HUVECs) and DPMSCs with tubule length formation and total branching points. Our meta-analysis revealed that oral-derived MSCs (dental pulp stem cells and SCAP) carry a better angiogenic potential in vitro than endothelial cell lines alone. The reviewed literature illustrates that oral cavity-derived MSCs (OC-MSCs) increased angiogenesis. The present literature reveals a dearth of investigations involving sources other than dental pulp. Even though OC-MSCs have revealed more significant potential than other MSCs, more comprehensive, target-oriented interinstitutional prospective studies are warranted to determine whether oral cavity-derived stem cells are the most excellent sources of significant angiogenic potential.

Assessment of angiogenic potential of mesenchymal stem cells derived conditioned medium from various oral sources.

Background: Abnormal angiogenesis hamper blood vessel proliferation implicated in various biological processes. The current method available to clinically treat patients to enhance angiogenesis is administering the angiogenic growth factors. However, due to a lack of spatiotemporal control over the substantial release of these factors, numerous drawbacks are faced such as leaky vasculature. Hence, stem-cell-based therapeutic applications are running their race to evolve as potential targets for deranged angiogenesis. In clinical dentistry, adequate tissue vascularization is essential for successful endodontic therapies such as apexogenesis and apexification. Furthermore, wound healing of the extraction socket and tissue regeneration post-surgical phase of treatment including implant placement require angiogenesis as a foundation for the ultimate success of treatment. Mesenchymal stem cells (MSCs) secrete certain growth factors and cytokines in the culture medium during the proliferation. These factors and cytokines are responsible for various biological activities inside human body. Oral cavity-derived stem cells can secrete growth factors that enhance angiogenesis. Aim: The aim of the study was to investigate the angiogenic potential of conditioned medium (CM) of MSCs derived from different oral sources. Methods: Oral tissues such as dental pulp of adult and deciduous teeth, gingiva, and buccal fat were used to isolate dental pulp MSCs (DPSCs), exfoliated deciduous teeth, gingival MSCs, and buccal fat derived MSCs. MSCs conditioned medium (CM) from passage four cells from all the sources were obtained at 48 h interval and growth factor analysis was performed using flow cytometry. To assess the functionality of the CM, Chick Yolk Sac Membrane (YSM) assay was performed. Results: CM obtained from DPSCs showed higher levels of vascular endothelial growth factor, fibroblast growth factor, and hepatocyte growth factor as evidenced by flow cytometry. Furthermore, DPSC-CM exhibited significantly higher pro-angiogenic potential when assessed in in-ovo YSM assay. Conclusion: DPSCs so far seems to be the best source as compare to the rest of oral sources in promoting angiogenesis. A novel source of CM derived from buccal fat stem cells was used to assess angiogenic potential. Thus, the present study shows that CM derived from oral cavity-derived-MSCs has a dynamic and influential role in angiogenesis. Relevance for Patients: CM derived from various oral sources of MSCs could be used along with existing therapies in medical practice where patients have compromised blood supply like in diabetes and in patients with debilitating disorders. In clinical dentistry, adequate tissue vascularization is essential for successful wound healing, grafting procedures, and endodontic therapies. DPSCs-CM shows better angiogenic potential in comparison with other oral sources of MSCs-CM. Our findings could be a turning point in the management of all surgical and regenerative procedures requiring increased angiogenesis.

Age Estimation in Children by the Measurement of Open Apices in Teeth: A Study in the Western Indian Population.

In forensic sphere and clinical dentistry, age estimation is a topic of utmost importance. Various techniques are employed in children to determine age; however, dental development has proven to be an appropriate method because of its low variability. Cameriere's method is a widely accepted method of age estimation in children, which is carried out by measuring the projections of open apices and also the heights of developing permanent teeth seen on panoramic radiographs. The aim of this study is to establish a new formula for age estimation in the Western Indian population by measuring the open apices of mandibular teeth using Cameriere's European formula. For this study, we included 311 panoramic radiographs of healthy children living in Western India (Maharashtra, Gujarat, and Goa) aged 4-15 years which were analysed by two independent researchers. Seven left permanent mandibular teeth were assessed for length and width of open apices. Dental maturity was evaluated using measurements of the left seven permanent mandibular teeth (x i = A i /L i , i = 1,…, 7), the sum of the normalized open apices (s), and the number (N0) of teeth with complete root formation. A linear relationship between open apices, N0, age, and other factors was evaluated with the aid of a stepwise multiple regression model. A stepwise linear regression showed that all parameters, gender, s, N0, and x 5, were significantly associated with age (R = 85%). No statistically significant difference was found between the predicted and actual chronological age of children in the age group of 4-13 years using the regression equation for the Western Indian population. The present research suggests that the new regression formula developed will be more accurate for age assessment in the Western Indian population.

Teledentistry: A Boon Amidst COVID-19 Lockdown-A Narrative Review.

The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease (COVID-19) has caused widespread public health concerns. Despite huge efforts to contain the disease spread, it is still on the rise because of the community spread pattern of this infection. In order to prevent the community spread, a nationwide lockdown was implemented, due to which many restrictions were imposed on movements of citizens within the country. Since the dental professionals were at the forefront of acquiring the infection, the majority of the dental clinics were shut for routine dental procedures. Only emergency treatment was provided to the patients. However, due to restrictions in movement, it was difficult for the patients to visit the clinics for routine check-ups. This was overcome by the advancements in technology which has a major impact on medicine. Due to increased usage of smartphones and related software applications, the clinical data exchange was facilitated between patients and clinicians which has been termed as "teledentistry." Teledentistry is a combination of telecommunications and dentistry, involving the exchange of clinical information and images for dental consultation and treatment planning. This technology served as a boon for the dentists to manage dental emergencies during the lockdown period. This narrative review discusses teledentistry and its applications in general and specialty dental practice amidst the COVID-19 lockdown.

COVID-19: Changing Trends and Its Impact on Future of Dentistry.

The outbreak of coronavirus disease 2019 (COVID-19) rapidly escalated into a worldwide pandemic, creating a global health and economic crisis. It is a novel virus which is distinct from SARS-CoV and MERS-CoV, with Chinese horseshoe bats being the most probable origin. Transmission occurs primarily through droplet spread or contact routes. Due to the characteristics of dental settings, the risk of cross infection between dental health care personnel (DHCP) and patients can be very high. This article provides a brief overview of the structure of the virus, modes of transmission, and clinical features of COVID-19 disease. The aim of this article is to recommend infection control strategies and patient management protocols to provide optimum dental care and simultaneously prevent nosocomial infection in dental settings.

Survival of Bonded Space Maintainers: A Systematic Review.

AIM: This systematic review was aimed at evaluating the average survival time and the various factors which determine the longevity of bonded space maintainers. BACKGROUND: Although a meta-analysis could not be performed from the available literature, this review emphasizes the various factors contributing to the success of bonded space maintainers and its relevance during the planning of bonded space maintainers. REVIEW RESULTS: The study selection criteria included in-vivo randomized and non-randomized clinical trials performed which was published in English. The databases searched were Pubmed, EBSCOhost and Google scholar, wherein the articles published from 1st January 1995 to 31st December 2015 were selected in the review. CONCLUSION: From the existing data, it can be concluded that the average survival period of bonded space maintainers is 11.2 months. However, there is a necessity for additional clinical trials with strict protocols to better the level of evidence. CLINICAL SIGNIFICANCE: From the various articles included in the review, the longevity of bonded space maintainers was found to be comparable to the banded space maintainers. Hence, the bonded space maintainers can be a suitable alternative to the banded space maintainers in pediatric dentistry.How to cite this article: Deshpande SS, Bendgude VD, Kokkali VV. Survival of Bonded Space Maintainers: A Systematic Review Int J Clin Pediatr Dent. 2018;11(5):440-445.

Percutaneous closure of aortic pseudoaneurysm in a young female with atrial septal occluder.

This case report represents a novel technique for the treatment of a pseudoaneurysm of the aorta. Pseudoaneurysm of the aorta has been reported in patients post heart surgery. This case report is about a patient who had a pseudoaneurysm most probably following tuberculosis. Traditionally, the treatment of choice is surgical correction; however, in the current era, there are case reports describing the use of either stent grafts or Amplatzer occluders for occlusion of the pseudoaneurysm in high-risk surgical cases. We performed successful closure of the aortic pseudoaneurysm using atrial septal occluder. .

Glycosaminoglycan measured from synovial fluid serves as a useful indicator for progression of Osteoarthritis and complements Kellgren-Lawrence Score.

BACKGROUND: Plain radiography is the first choice for diagnosis and monitoring of knee-osteoarthritis (OA) while, Kellgren-Lawrence score (KL) is most widely used to grade OA severity. However, incompetency for reproducibility of joint space measurement in longitudinal assessment and non-linearity of KL-score system, limits radiography-based early diagnosis of the disease. Glycosaminoglycan (GAG) is direct cartilage-degradation product, which can be measured biochemically. We strived to correlate KL-score and GAG from OA patients to compliment KL-system. METHODS: We obtained 34 synovial-fluid (SF) samples from 28 OA patients (few bilateral) with different disease severity using arthrocetesis. All patients were categorised using radiographic KL-score-system. SFs were further analysed for GAG estimation using 1,2-dimethylmethylene blue (DMMB) assay. RESULTS: A substantial increase in GAG was noted in KL-grade-II and III, comparing grade-I patients, indicating amplified cartilage-degradation. KL-grade-IV patients revealed further rise in GAG reflecting more cartilage-loss. Another category of grade-IV patients with lower GAG were also detected, indicating close to total cartilage-loss. CONCLUSIONS: Accurate diagnosis of cartilage-loss remains a challenge with OA due to limitations of KL-system; thus no target intervention is available to arrest active cartilage-loss. We propose, GAG-estimation in OA patients, characterizes accurate biochemical depiction of cartilage degeneration. GENERAL SIGNIFICANCE: Radiology often fails to reveal an accurate cartilage loss, associated with OA. GAG levels from the SFs of OA patients' serve as a useful marker, which parallels cartilage degeneration and strengthen radiographic grading system, ultimately.

Inflammatory response of cultured rat synoviocytes challenged with synovial fluid from osteoarthritis patients correlates with their radiographic grading: a pilot study.

The inflammatory nature of synovial fluid (SF) of varying grade osteoarthritis (OA) patients was estimated by measuring pro-inflammatory factors and through a unique cell-challenge experiment. SF samples were collected from six OA and one non-OA patient; spanning Kellgren-Lawrence (KL) grades were analyzed for interlukin-1-beta (IL-1ß), nitric oxide (NO) and its derivatives, and glycosaminoglycan (GAG). Levels of IL-1ß, NO, and GAG in SF did not correlate with KL grades of the patients studied. In the cell-challenge experiment, cultured rat synoviocyte fibroblasts (RSFs) were challenged by the patient's SFs with and without pre-treatment of IL-1ß and lipopolysaccharide (LPS). NO released by the cells was taken as an indicator of inflammation. SFs from KL grades 2 and 3 induced maximum inflammation in cultured RSFs (grade 2 64.61 ± 4.8 and 89.51 ± 5.6 µM/ml after 48 and 72 h, grade 3 58.27 ± 2.7 and 64.22 ± 2.8 µM/ml after 48 and 72 h, respectively). Similar trend was observed in RSF pretreated with either recombinant IL-1ß or LPS suggesting that SF from patients KL grades 2 and 3 accumulates more pro-inflammatory factors. IL-1ß-pre-treated RSFs challenged by SF for 72 h showed 234.41 ± 17.6 µM/ml increase (patient 3, grade 3), whereas higher NO after LPS pre-treatment was recorded (118.92 ± 6.2 µM/ml; patient 3, grade 3). Interestingly, SFs from grade 1 and non-OA patient could reduce released NO to 27.10 ± 2.2 µM/ml showing potency to alleviate inflammation. These interesting findings, however, need to be confirmed on a wider number of patients, which may offer significant therapeutic application in treatment of OA.

Meniscal tear as potential steering factor for inflammation may aggravate arthritis: two case reports.

INTRODUCTION: Meniscal tear is thought to play a crucial role in onset as well as progression of arthritis. However, role of cytokine response to meniscal injury and resulting inflammation is not clearly understood. Because synovial fluid is juxtaposed to cartilage and serves as a biological connection between chondrocytes and synoviocytes, we chose synovial fluid analysis to ascertain biochemical response associated with a meniscal tear. CASE PRESENTATION: We report the cases of two patients with clinically different inflammatory arthritis, both of whom are Indian men. Patient 1 was 30 years of age, and patient 2 was 50 years of age. They both had a history of meniscal tear, which we confirmed by magnetic resonance imaging scans. Synovial fluid samples obtained from these two patients were analyzed for proinflammatory markers, such as interleukin 1ß (IL-1ß) and nitric oxide, and also for glycosaminoglycan as a cartilage degradation indicator. Relatively high levels of IL-1ß (2000.0 ± 15.7 pg/ml) and nitric oxide (4.73 ± 0.05 µM/ml) and relatively low glycosaminoglycan (93.75 ± 6.3 µg/ml) were observed in patient 1, corroborating the diagnosis of traumatic meniscal tear. Compared to patient 1, Patient 2 had relatively low levels of IL-1ß (54.55 ± 14.5 pg/ml) and nitric oxide (20.00 ± 0.6 µM/ml) and remarkably high glycosaminoglycan levels (553.33 ± 1.7 µg/ml), coupled with significant osteophytes and profound cartilage loss, which indicated severe arthritis and a diagnosis of degenerative meniscal tear. CONCLUSION: The elevated levels of inflammatory IL-1ß aggravated the severity of arthritis attributable to meniscal tear in both patients, as found in follow-up visits. This was quite evident in patient 2, whereas patient 1, being younger, had less serious symptoms. Meniscal tear has emerged as a potential confounding factor in arthritis with different clinical backgrounds, which leads to increased levels of inflammation and results in accelerated disease progression.

Short term analysis of healed post-tubercular kyphosis in younger children based on principles of congenital kyphosis.

BACKGROUND: The patients with healed severe progressive tubercular kyphosis may develop late-onset paraplegia. A particular subgroup of these children (Type IB progression) may benefit from the management principles of congenital kyphosis. Self-correction may be observed by selective continued growth of anterior vertebral epiphyseal end-plates over the posterior fused mass. We report a series of cases with posterior fusion of progressive post-tubercular kyphosis with an aim to prevent further progression of kyphosis and to assess if any gradual self correction is seen in followup. MATERIALS AND METHODS: Twelve children fulfilling inclusion criteria of clinicoradiological, hematological diagnosis of healed spine TB having no or <2 spine at risk signs having documented progression of kyphosis and neural deficit underwent posterior fusion in situ without instrumentation, using autogenous iliac crest grafts as well as allograft donor bone graft. They were followed up to maximum of 5 years. RESULTS: All 12 children had a progressive increase in angle preoperatively. Mean followup was 3.6 years. Post surgery, 66% showed a clinical improvement and correction, 25% had static angle, and worsening in one patient. Thus, overall 91% have a favorable result. CONCLUSION: The mechanism of correction of deformity in presence of posterior fusion is continued growth of the anterior epiphyseal end plates and hence this leads to selective differential anterior column growth giving gradual correction of kyphosis. This avoids anterior, technically demanding and complex, internal gibbus surgeries. This procedure is simple, safe, and less morbid with good results, avoiding long term disability to the patients in selected group of patients.

Circulating cytokine profiles in leprosy patients.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae which is an obligate intracellular pathogen. It is characterised by a broad spectrum of clinical forms dictated by the patient's immune response to the organism. The tuberculoid pole has good cell mediated immunity to M. leprae, with few lesions and bacilli while the lepromatous pole has poor immunity coupled with extensive involvement and greater bacillary load. METHODS: We studied serum levels of interferon gamma and interleukin 6 in 100 patients of untreated leprosy, compared them with 30 age and sex matched normal healthy controls and co-related them with different parts of the spectrum and reactional episodes. The purpose of this study was to delineate the role of cytokines and their clinical implications in the leprosy spectrum and during reactional episodes. RESULTS: We observed that mean cytokine levels were significantly higher in the patient group as compared to the controls. In the non reactional patient group, pure neuritic leprosy patients showed highest levels of INFgamma which were directly proportional to the extent of nerve involvement. Lepromatous leprosy patients had the highest levels of IL6. Bacteriological index demonstrated a negative and positive corelation with INFgamma and IL 6 levels respectively. Type I and Type II reactional patients had higher levels of INFgamma and IL 6 respectively as compared to nonreactional patients. CONCLUSIONS: Our results suggest that pure neuritic leprosy and borderline tuberculoid patients in type I reaction are at greatest risk for nerve and tissue damage. Thus cytokines have the potential to play a significant role in classification, prognosis and treatment of leprosy.

A study of serum nitric oxide levels in psoriasis.

BACKGROUND: M any inter and intracellular mediators have been implicated in the pathogenesis of psoriasis. Nitric oxide has been shown to play an important role in many diseases. Previous studies have demonstrated raised levels of nitric oxide in psoriatic plaques which may be attributed to its effect on keratinocytes, on local cGMP levels or its ability to induce angiogenesis. AIMS: To detect serum nitric oxide (NO) levels in patients with active psoriasis, to correlate these levels with severity of disease and compare them with those in normal individuals. METHODS: Thirty six patients with active psoriasis were selected after written consent. All patients on topical or systemic treatment for fifteen days prior to the study were excluded. Disease severity was assessed by PASI score and serum nitric oxide levels were detected by Greiss method and compared with age and sex matched controls. Statistical analysis of all data was done by unpaired t test. RESULTS: Out of 36 patients, 30 had chronic plaque psoriasis (mean NO 157.5), 4 had erythroderma (mean NO 120.2) and 2 had generalized pustular psoriasis (mean NO 144.3). The mean NO level in the psoriatic group was 157.7 with SD 50.4 while in the control group it was 32.8 with SD 4.03. The difference was statistically significant (t=13.8, P < 0.001). In the chronic plaque group, as the duration of disease increased, the NO levels increased significantly. CONCLUSIONS: Nitric oxide levels were significantly increased in patients with psoriasis and these levels showed a positive correlation with severity and duration in the chronic plaque type group.