Clinical update on the use of mesenchymal stem cells in COVID-19.

The COVID-19 pandemic has evoked the scientific community to combine all efforts needed to find a cure for the disease. With the limited therapeutic effects of pharmacological therapies, attention has been drawn to alternative ones such as stem-cell based therapy particularly with mesenchymal stem cells (MSCs). Recently, a large number of clinical trials are ongoing to evaluate the safety and efficacy of MSCs in patients with COVID-19; however, only very few data are released. Thereby, we anxiously await the results of FDA-approved trials to provide more definitive data on the use of MSCs in COVID-19 patients, especially the critically ill. Herein, we shed light on the therapeutic agents that have been tested and used for the treatment of COVID-19 and provide an insight into MSC-based approaches for COVID-19 at both preclinical and clinical levels.

Effect of Adipose derived mesenchymal stem cells on multiple Organ Injuries in diet-induced obese mice.

Background: Obesity is a complex disease involving the accumulation of body fat that can inflict a substantial risk to health due to the potent role it plays in the development of a series of chronic diseases including cardiovascular diseases (CVD), nonalcoholic fatty liver diseases (NAFLD), kidney diseases, diabetes, and some cancers. Despite all efforts made, no therapy has succeeded in reversing the obesity pandemic and its associated diseases. Herein, the aim was to study the effect of adipose-derived mesenchymal stem cells on obesity-induced multi-organ injuries in a diet-induced obese mouse model. Male C57BL/6 mice were fed with regular chow diet or high fat diet (HFD) to induce obesity for 15 weeks after which the mice were administered two doses of adipose-derived mesenchymal stem cells (ASC-treated groups) or media as control (media-treated groups). Animals were sacrificed and adipose, hepatic, renal, and cardiac tissues were obtained for histopathological evaluation. Mice on HFD showed excessive pathological alterations such as epididymal adipose tissue expansion, hepatic fat accumulation, glomerular swelling, and cardiomyocyte hypertrophy. However, treatment with ASCs significantly reversed the significant histopathological abnormalities induced by obesity. In conclusion, this study demonstrated the therapeutic effects of adipose-derived mesenchymal stem cells on obesity-associated complications such as NAFLD, CVD, and kidney disorders in a diet-induced obese animal model, which were partly due to the attenuation of inflammatory cytokines such as TNF-α and IL-6.

The therapeutic effects of adipose-derived mesenchymal stem cells on obesity and its associated diseases in diet-induced obese mice.

Obesity is a global public health concern associated with increased risk of several comorbidities. Due to the limited effectiveness of current therapies, new treatment strategies are needed. Our aim was to examine the effect of adipose-derived mesenchymal stem cells (AD-MSCs) on obesity and its associated diseases in a diet-induced obese (DIO) animal model. C57BL6 mice were fed with either high fat diet (HFD) or CHOW diet for 15 weeks. Obese and lean mice were then subjected to two doses of AD-MSCs intraperitoneally. Mice body weight and composition; food intake; blood glucose levels; glycated hemoglobin (HbA1c), intraperitoneal glucose tolerance test and atherogenic index of plasma (AIP) were measured. Pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were also determined. AD-MSCs treatment reduced blood glucose levels, HbA1c and AIP as well as improved glucose tolerance in DIO mice. In addition, MSCs caused significant attenuation in the levels of inflammatory mediators in HFD-fed mice. Taken together, AD-MSCs were effective in treating obesity-associated diabetes in an animal model as well as protective against cardiovascular diseases as shown by AIP, which might be partly due to the attenuation of inflammatory mediators. Thus, AD-MSCs may offer a promising therapeutic potential in counteracting obesity-related diseases in patients.

Conventional and Alternative Mesenchymal Stem Cell Therapies for the Treatment of Diabetes.

Diabetes is a public health problem affecting millions of people around the world. Despite the availability of many antidiabetic medications, the adequate level of control of the disease and management of diabetic patients remain a huge challenge. Because of the limitations of current therapies and the tremendous potential of non-conventional treatments such as stem cell therapy, herein, we review the applications of mesenchymal stem cells (MSCs) in treating diabetes. Owing to their unique regenerative and immunomodulatory properties, MSCs have been widely utilized in numerous applications both in animal models and human clinical trials for the treatment of diabetes. This review will summarize the latest experimental and clinical studies that have provided evidence of the beneficial role of MSCs in diabetes treatment.

Three-Dimensional Cell Culture Models to Study Respiratory Virus Infections Including COVID-19.

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.

Antihyperglycemic and hepatoprotective properties of miracle fruit (Synsepalum dulcificum) compared to aspartame in alloxan-induced diabetic mice.

OBJECTIVE: This study was undertaken to investigate the antihyperglycemic potential of miracle fruit (MF) as well as its hepatic safety as compared to aspartame in alloxan-induced diabetic mice. METHODS: MF extracts were prepared and screened for their phytochemical composition using high-performance liquid chromatography (HPLC). Total phenolic, flavonoid and tannin contents and antioxidant potential were also determined. Additionally, MF was evaluated for its sensory attributes. For in vivo work, MF ethanol extract at high (MFH: 500 mg/kg body weight [BW]) and low (MFL: 250 mg/kg BW) doses as well as aspartame were injected intraperitoneally into alloxan-induced diabetic mice. Blood glucose levels were determined following acute and subchronic treatment. At the end of the study, animals were sacrificed, serum was collected for biochemical analysis and liver tissues were obtained for histopathological examination. RESULTS: MF ethanol extract contained more flavonoids and tannins, and had higher 1,1-diphenyl-1-picrylhydrazyl radical-scavenging activity (79.61%) compared to MF aqueous extract (P < 0.05). HPLC analysis of MF ethanol extract also revealed the presence of 10 antioxidants with quercetin comprising the major polyphenol. Additionally, sensory analysis of MF showed that its intake is effective in masking undesirable sourness. Subchronic administration of MFH proved amelioration of hyperglycemia in mice as compared to aspartame. Moreover, aspartame treatment significantly elevated (P < 0.05) the level of alanine aminotransferase and had destructive effects on the liver histopathology; however, hepatic architecture was restored by low and high doses of MF. CONCLUSION: MF is an effective antihyperglycemic with hepatoprotective properties that can be used as a healthier alternative sweetening agent in place of aspartame for sour beverages.

Gastroprotective and anti-inflammatory effects of Prunus cerasus phytochemicals and their possible mechanisms of action.

Prunus cerasus (P. cerasus) is an alternative-medicine used traditionally for amelioration of chronic-ailments marked by elevation in oxidative-stress like neuropathy. The oxidative-stress control was reported to ameliorate the inflammatory-process. This study aimed to phytochemically-investigate P. cerasus most-active phytochemicals utilizing in-vivo biological models to explore their gastroprotective, anti-inflammatory, and antinociceptive potentials and their possible mechanisms of action. Sonication with EtAc was used to extract P. cerasus fruit (Scf), and seed (Scs). The phytochemical-investigation of Scf was performed by RP-HPLC, while that of Scs was explored utilizing GC-FID. A bio-guided-fraction and isolation method was done utilizing column-chromatography, and have shown that cyanidin-3-glucoside (Cy3G) was the most-active constituent in Scf, while linoleic-acid (LA) was the most-active constituent in Scs. Scf, Scs, Cy3G, and LA significantly (p ˂ 0.05) protected the gastric-mucosa against HCl/EtOH-induced gastric-lesions. Scs (200 mg/kg) has shown the most gastroprotective-potentials, and had comparable-results to ranitidine (50 mg/kg). Scf, Scs, Cy3G, and LA have shown significant anti-inflammatory and antinociceptive potentials against carrageenan induced-edema and nociceptive-pain, respectively, where Scs (200 mg/kg) has shown the most anti-inflammatory and antinociceptive potentials, and had comparable results to ibuprofen (100 mg/kg). Scf, Scs, Cy3G, and LA have counter-acted carrageenan-induced oxidative-stress markers, with increased serum-catalase and reduced-glutathione levels, and decreased lipid-peroxidation. Histopathological-studies demonstrated gastroprotective potentials, regeneration and improvement of the spleen-structural architecture when treated with highest doses of Scs and Scf. The reduction of the pro-inflammatory TNF-alpha and IL-6, and elevation the anti-inflammatory factor IL-10 levels, spleen regenerative-capacity and oxidative-stress amelioration might be the main-mechanism responsible for P. cerasus anti-inflammatory potentials. P. cerasus appears to aid in ameliorating the inflammatory process, and reducing pain-thresholds while preserving the stomach.

A Review on Acrylamide in Food: Occurrence, Toxicity, and Mitigation Strategies.

Acrylamide (AA) is a food contaminant present in a wide range of frequently consumed foods, which makes human exposure to this toxicant unfortunately unavoidable. However, efforts to reduce the formation of AA in food have resulted in some success. This review aims to summarize the occurrence of AA and the potential mitigation strategies of its formation in foods. Formation of AA in foods is mainly linked to Maillard reaction, which is the first feasible route that can be manipulated to reduce AA formation. Furthermore, manipulating processing conditions such as time and temperature of the heating process, and including certain preheating treatments such as soaking and blanching, can further reduce AA formation. Due to the high exposure to AA, recognition of its toxic effect is necessary, especially in developing countries where awareness about AA health risks is still very low. Therefore, this review also focuses on the different toxic effects of AA exposure, including neurotoxicity, genotoxicity, carcinogenicity, reproductive toxicity, hepatotoxicity, and immunotoxicity.

COVID-19: Test, Test and Test.

A new virus was identified in late December 2019 when China reported the first cases of pneumonia in Wuhan, and a global COVID-19 pandemic followed. The world was not late to respond, with a number of sweeping measures ranging from social distancing protocols, stringent hygienic practices, and nation-wide lockdowns, as well as COVID-19 testing campaigns in an attempt to prevent the transmission of the disease and contain the pandemic. Currently, different types of diagnostic testing have been adopted globally, such as nucleic acid detection tests, immunological tests and imaging approaches; however, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) remains the "gold standard" for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pre-analytical factors, such as specimen selection and collection, are crucial for RT-PCR, and any suboptimal collection may contribute to false-negative results. Herein, we address some of the specimen types that have been used in molecular detection methods for COVID-19. However, the pandemic is still evolving, and information might change as more studies are conducted.

Knowledge and Attitude Among Lebanese Pregnant Women Toward Cord Blood Stem Cell Storage and Donation.

Background: Umbilical cord blood (UCB) used to be considered waste material and was discarded at birth. However, cord blood is now considered a rich source of adult stem cells that can be used to treat many conditions and diseases. This study was performed to determine pregnant women's knowledge and attitudes toward cord blood stem cell banking and donation in Lebanon. Methods: A descriptive study was conducted in antenatal clinics in Beirut and data were collected using a questionnaire distributed to pregnant women after provision of informed consent. A total of 244 women responded. Results: Less than half of the women (46%) reported knowledge about cord blood banking. However, participants with university and secondary education had significantly higher odds of considering UCB storage compared to those with primary education (odds ratio (OR) 8.62, 95% confidence interval (CI) 2.74-27.15 and OR 21.23,95% CI 6.55-68.86, respectively). Older pregnant women were less likely to think about UCB stem cells storage (OR 0.92, 95% CI 0.85-0.98). Conclusion: Respondents who had an existing knowledge about UCB stem cells banking in general were more likely to consider storing UCB in blood banks if affordable (45.9%). Therefore, it is necessary to inform pregnant women about stem cell banking so that they can make the appropriate decisions for themselves.

Infrared-Assisted Extraction and HPLC-Analysis of Prunus armeniaca L. Pomace and Detoxified-Kernel and their Antidiabetic Effects.

INTRODUCTION: Prunus armeniaca L. (P. armeniaca) is one of the medicinal plants with a high safety-profile. OBJECTIVES: The aim of this work was to make an infrared-assisted extraction (IR-AE) of P. armeniaca fruit (pomace) and kernel, and analyse them using reverse phase high-performance liquid chromatography (RP-HPLC) aided method. METHODS: IR-AE is a novel-technique aimed at increasing the extraction-efficiency. The antidiabetic-potentials of the P. armeniaca pomace (AP) and the detoxified P. armeniaca kernel extract (DKAP) were monitored exploring their possible hypoglycemic-mechanisms. Acute (6 h), subchronic (8 days) and long-term (8 weeks) assessment of Diabetes mellitus (DM) using glucometers and glycated hemoglobin (HbA1c) methods were applied. RESULTS: Serum-insulin levels, the inhibitory effects on alpha-glucosidase, serum-catalase (CAT) and lipid peroxidation (LPO) levels were also monitored. AP was shown to be rich in polyphenolics like trans-lutein (14.1%), trans-zeaxanthin (10.5%), trans-ß-cryptoxanthin (11.6%), 13, cis-ß-carotene (6.5%), trans 9, cis-ß-carotene (18.4%), and ß-carotene (21.5%). Prunus armeniaca kernel extract before detoxification (KAP) was found to be rich in amygdaline (16.1%), which caused a high mortality rate (50.1%), while after detoxification (amygdaline, 1.4%) a lower mortality rate (9.1%) was found. AP showed significant (p ≤ 0.05, n = 7/group) antidiabetic-activity more prominent than DKAP acutely, subchronically and on longer-terms. IR-AEs displayed more efficient acute and subchronic blood glucose level (BGL) reduction than a conventional extraction method, which might be attributed to IR-AE superiority in extraction of active ingredients. AP showed more-significant and dose-dependent increase in serum-insulin, CAT-levels and body-weights more prominent than those of DKAP. Alpha-glucosidase and LPO levels were inhibited with AP-groups more-significantly. CONCLUSION: In comparison to conventional-methods, IR-AE appeared to be an efficient and time-conserving novel extraction method. The antidiabetic-potentials of pomace and detoxified-kernels of P. armeniaca were probably mediated via the attenuation of glucose-provoked oxidative-stress, the inhibition of alpha-glucosidase and the marked insulin-secretagogue effect. Copyright © 2017 John Wiley & Sons, Ltd.

Hypoglycemic effects of Prunus cerasus L. pulp and seed extracts on Alloxan-Induced Diabetic Mice with histopathological evaluation.

AIM OF THE STUDY: The study was undertaken to investigate the acute and subchronic hypoglycemic effects of an ethyl acetate (EtAc) extract of red sour cherry (Prunus cerasus) pulps and seeds in alloxan-induced diabetic mice. MATERIALS AND METHODS: The Prunus cerasus pulp (PPc) and seed (SPc) EtAc extract s were IP-administered to the mice in doses of 100, 150 and 200mg/kgbody weight (b.w.) for acute study (6h) and subchronic study (8days). The in vivo effects of (PPc) and (SPc) EtAc extracts were assessed through blood glucose levels (BGL), changes in body weight as well as antioxidant enzyme activity. At the end of the study, animals were sacrificed for obtaining pancreatic tissues samples to assess histopathological changes in pancreas of control and alloxan-induced mice. RESULTS: Acute administration of either PPc or SPc for 6h at all tested doses, significantly (P≤0.05) decreased BGL as compared with vehicle treated diabetic control (DIA CTRL) group with PPc showing more significant acute antidiabetic activity than those of SPc. In addition, subchronic administration of PPc has shown more significant (P≤0.05) amelioration of hyperglycemia, weight-loss and oxidative stress at all doses compared to SPc administration. Histologically, treatment with PPc and SPc showed significant pancreatic cell regeneration compared to diabetic controls. CONCLUSIONS: Results indicated that ethyl acetate extracts of Prunus cerasus pulps and seeds promote acute and subchronic hypoglycaemic effects in alloxan-induced diabetic mice with pulp extracts having a more pronounced effect.

Three-dimensional in vitro culture techniques for mesenchymal stem cells.

In recent years there has been a growing interest in culturing adherent cells using three-dimensional (3D) techniques, rather than more conventional 2D culture methods. This interest emerges from the realization that growing cells on plastic surfaces cannot truly re-create 3D in vivo conditions and therefore might be limiting the cells' potential. In addition, adult stem cells exist in specialized microenvironments, or niches, where the spatial organization of different niche elements (such as different cell types, extracellular matrix) contributes significantly to stem cell maintenance, which cannot be represented using 2D in vitro models. We have generated a range of different 3D approaches for the analysis of mesenchymal stem cells (MSCs) using both mono- and co-culture environments.

Turning round: multipotent stromal cells, a three-dimensional revolution?

Mesenchymal stromal cells (MSC) can be isolated from adult tissues and induced to differentiate into skeletal cells, such as osteoblasts, chondrocytes and adipocytes. Consequently, ex vivo MSC are valuable systems for studying the mechanisms that control tissue-context lineage commitment and may offer broad therapeutic applications in the orthopedic theater and beyond. To date, most of these studies have used MSC grown on two-dimensional (2-D) plastic surfaces. The use of three-dimensional (3-D) in vitro growth techniques for MSC may accelerate these areas of research by providing a more representative 'in vivo-like' environment, where cells interact with each other and their cellular products, rather than a plastic surface. We introduce some of the techniques used for 3-D in vitro cultures and how they relate to the MSC field. We will present evidence of how MSC grown as 3-D spheroids not only permits appropriate MSC-like behavior, but appears to promote their stem-cell attributes and therapeutic benefit in applications ranging from regenerative medicine to anti-inflammatory treatments and cancer therapy. 3-D culture techniques also allow de/reconstruction of the specialized in vivo niche of the tissue-resident stem cell where microenvironmental influences can be recognized.

Regulation of mesenchymal stem cell activity by endothelial cells.

Emerging data suggest that mesenchymal stem cells (MSCs) are part of a periendothelial niche, suggesting the existence of heterotypic cell-cell crosstalk between endothelial cells and MSCs that regulate MSCs in their local microenvironment. We determined the effects of paracrine factors secreted by human umbilical vein endothelial cells (HUVECs) on MSC survival, proliferation, and differentiation by using an optimized, serum-free HUVEC-conditioned medium (CM). HUVEC-CM induced a significant increase in the size and number of colony-forming units-fibroblast (CFU-F) and CFU-osteoblast (CFU-O) and stimulated the proliferation of MSCs as determined by 5-bromo-2'-deoxyuridine incorporation, compared with non-CM. We also demonstrated that CM significantly enhanced the osteogenic differentiation of MSCs as shown by alkaline phosphatase enzyme histochemistry and von Kossa staining of mineralized nodules as well as by quantitative reverse transcriptase-polymerase chain reaction analysis of osteogenic markers. In contrast, there was no effect on the adipogenic differentiation of MSCs. Bioinformatic integration of HUVEC and MSC gene expression datasets identified several candidate signaling pathways responsible for mediating these effects, including fibroblast growth factor, Wnt, bone morphogenetic protein, and Notch. These data suggest strongly that endothelial cells secrete a soluble factor (or factors) that stimulates progenitor cell activity and, selectively, the osteogenic differentiation of MSCs that could contribute to niche exit.