American journal of stem cells最新文献

Background: Autologous adipose-derived stromal vascular fraction (SVF) is an emerging therapy that is being pioneered as a potential treatment for keloids and hypertrophic scars. Up to this point, there isn't a cure for keloids and hypertrophic scars yet they comprise the commonest benign skin disorders. Despite published studies reporting potential therapeutic benefits of SVF, their use and efficacy on scar improvement are not clearly described. The aim of this review is to describe the clinical practice involved in harvesting, processing, utilization of SVF, and associated efficacy in scar treatment.

Methods: We shall include published clinical articles evaluating the efficacy of SVF on improving scar characteristics and assessment scores among adults with keloids or hypertrophic scars. Article search of Medline/PubMed, Cochrane Library and Embase using Mesh terms of "scars" and "stromal vascular fraction" combined with the Boolean operators ("AND", "OR") will be performed by two independent researchers following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. The primary outcome measure will be the mean difference in the Scar characteristics including Scar assessment scores, scar thickness among others.

Data synthesis: Descriptive data synthesis and mean differences between treatment arms will be calculated for the primary outcome of the scar assessment scores. In case more than three studies provide consistent characteristics of the scar assessment scores, a meta-analysis will be conducted.

Discussion: Evidence obtained from the systematic review will form the foundation upon which further clinical trials research will be conducted in evaluating the efficacy of autologous adipose-derived stromal vascular fraction in keloid and hypertrophic scar. The systematic review has been submitted to the PROSPERO database and is currently under review.

Objective: Mesenchymal stem cells can serve as a therapeutic option for COVID-19. Their immunomodulatory and anti-inflammatory properties can regulate the exaggerated inflammatory response and promote recovery of lung damage.

Method: Phase-1, single-centre open-label, prospective clinical trial was conducted to evaluate the safety and efficacy of intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in moderate COVID-19. The study was done in 2 stages with total 20 patients. Herein, the results of stage 1 including first 10 patients receiving 100 million cells on day 1 and 4 with a follow up of 6 months have been discussed.

Results: No adverse events were recorded immediately after the administration of MSCs or on follow up. There was no deterioration observed in clinical, laboratory and radiological parameters. All symptoms of the study group resolved within 10 days. Levels of inflammatory biomarkers such as NLR, CRP, IL6, ferritin and D-dimer improved in all patients after intervention along with improved oxygenation demonstrated by improvement in the SpO2/FiO2 ratio and PaO2/FiO2 ratio. None of the patients progressed to severe stage. 9 out of 10 patients were discharged within 9 days of their admission. Improvements were noted in chest x-ray and chest CT scan scores at day 7 in most patients. No post-covid fibrosis was observed on chest CT 28 days after intervention and Chest X ray after 6 months of the intervention.

Conclusion: Administration of 100 million mesenchymal stem cells in combination with standard treatment was found to be safe and resulted in prevention of the cytokine storm, halting of the disease progression and acceleration of recovery in moderate COVID-19. This clinical trial has been registered with the Clinical Trial Registry- India (CTRI) as CTRI/2020/08/027043. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=43175.

Objectives: This study aimed to investigate the effect of TGF-B1-transfected adipose-derived mesenchymal stem cell (AD-MSC) conditional medium (TGF-B1-CM) on CD44 expression and biological activities in MCF-7 and MDA-MB-231 cells.

Methods: In the study, the experimental groups were created as a standard medium, AD-MSC-CM, TGF-B1-CM, and TGF-B1 recombinant protein. The medium and proteins specified in these groups were applied to MCF-7 and MDA-MB-231 cells separately at 24, 48 and 72 hours. Western blot and immunofluorescent staining were performed with antibodies suitable for CD44 and canonical smad signaling pathway analyses between groups. Cellular proliferation in MCF-7 and MDA-MB-231 cells was measured by MTT. Biological activity analyses such as apoptosis, cell cycle, proliferation, DNA damage, and membrane depolarization between groups were tested on the Muse Cell Analyzer using appropriate kits. Cellular migration between groups was determined by showing cells that migrated to the scar area with in vitro scar formation. Statistics were performed with GraphPad Prism 8.02 software.

Results: It was determined that TGF-B1-CM activates the smad signaling pathway in MCF-7 and MDA-MB-231 cells. TGF-B1-CM increased pSMAD2/3 expression and decreased SMAD4 expression in breast cancer cells. A decrease in CD44 expression was found at points of increase in pSMAD2/3 expression. Decreased expression of SMAD4 in breast cancer cells with TGF-B1-CM was associated with decreased expression of CD44. In MCF-7 and MDA-MB-231 cells, TGF-B1-CM was found to increase apoptosis, decrease proliferation, disrupt membrane depolarization, and arrest cells at G0/G1 stage. TGF-B1-CM suppressed MCF-7 and MDA-MB-231 migrations.

Conclusion: SMAD4-targeted therapeutic strategies may be considered to suppress CD44 expression in breast cancer cells. Both the anti-tumorigenic factors released by AD-MSCs and the secretomes obtained as a result of supporting these factors with the overexpression of TGF-B1, severely suppressed breast cancer cells. With this study, it was planned to obtain a targeted biological product that suppresses breast cancer cells in vitro.

Objectives: This study aimed to investigate the induction effects of methanolic extracts of Nigella sativa (NiS), Brassica Oleracea (BrO), and Oenothera biennia (Obi) on transgenic embryonic stem cells (ESCs) and to evaluate the ability of germ cells (GCs) production using these pluripotent cells.

Methods: ESCs were amplified using a feeder layer. Embryoid bodies enzymatically dissociated to single cells and induced the extracts in gelatinized plates. Then RNA extraction and cDNA synthesis were performed. In the presence of appropriate primers, the desired genes were quantitatively evaluated by quantitative polymerase chain reaction (qPCR).

Results: The copies of all genes in the control group showed a decreasing trend during the first to third weeks. Compared to the control group, the expression level of sex determining region Y-box 2 gene (Sox2) showed the highest level. All four evaluated genes increased in all Obi groups compared to the control group. There is also a slight increase in the Nanog homeobox gene (Nanog). Obi extract in different concentrations has increased the expression of the Sox2 gene. Increased expression of this gene along with octamer-binding transcription factor 4 gene (Oct4) and Nanog indicates a condition close to germ cell-like cells (GCLCs).

Conclusions: According to the results of this study, NiS can increase expression of the Oct4, Sox2, Nanog, and stimulated by retinoic acid gene 8 (STRA8) genes and so increase the hope of GCs production. Storage of cells for 21 days in the presence of the extract compared to 14 days has a negative effect on cell growth and differentiation. The effects of meiosis onset and GCs production can be expected in the presence of some herbal extracts. Optimal utilization of these extracts requires further study in the field of different extracts and fractions of each extract to more effectively and purposefully direct the differentiation of stem cells.

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) started in December 2019 and affected the whole world in a short time. The course of the disease depends on the person's immune system, physical properties, health status, etc. as it varies according to its characteristics while it is asymptomatic in some people, it causes fatal processes that start with flu-like symptoms such as cough, fever, respiratory distress in some people and progress to acute respiratory distress syndrome (ARDS), severe pneumonia and multi-organ dysfunction, and the basic mechanism underlying these effects known as a cytokine storm. There is no specific effective antiviral drug or vaccine in treatment yet. Supportive/alternative treatment methods are needed as both the desired effect cannot be achieved and undesirable side effects are seen with the current treatments used in the clinic. Mesenchymal stem cells (MSCs) are frequently preferred recently from basic studies to clinical studies and are effective and safe in immune-mediated inflammatory diseases such as Systemic Lupus Erythematosus, Graft-versus-Host disease. MSCs can secrete many types of cytokines through paracrine secretion or directly interact with immune cells leading to immunomodulation. According to the results of the completed studies; it has been stated that the cytokine storm caused by the overstimulation of the immune system decreases and even damage of the cytokine storm on organs decreases, respiratory distress is relieved and contributes to the healing process by repairing damaged tissues. In this review, clinical trials completed/ongoing on MSCs recommended for treating COVID-19, a global problem, are reviewed and the review is prepared to specify the existence of such a route to clinicians.

Background and objectives: Drug delivery by nebulization has become a crucial strategy for treating different respiratory and lung diseases. Emerging evidence implicates stem cell therapy as a promising tool in treating such conditions, not only by alleviating the related symptoms but by improving the prognosis. However, delivery of human peripheral blood-derived stem cells (hPBSCs) to the respiratory airways remains an innovative approach yet to be realized. This study is an analytic, translational, and in vitro research to assess the viability and morphological changes of identified cell populations in hPBSCs cocktail derived from COVID-19 patients.

Methods and results: Peripheral blood (PB) samples were obtained from patients enrolled in the SENTAD-COVID Study (ClinicalTrials.gov Reference: NCT04473170). hPBSCs cocktails (n=15) were provided by the Cells Processing Laboratory of Abu Dhabi Stem Cells Center, and were nebulized by three different methods of nebulization: compressor (jet), ultrasonic, and mesh. Our results reported that nucleated CD45^dim cell count was significantly lower after the three nebulization methods, but nucleated CD45^- cells show a significant decrease only after mesh nebulization. Mesh-nebulized samples had a significant reduction in viability of both CD45^dim and CD45^- cells.

Conclusions: This study provides evidence that stem cells derived from PB of COVID-19 patients can be nebulized without substantial loss of cell viability, cell count, and morphological changes using the compressor nebulization. Therefore, we recommend compressor nebulizers as the preferable procedure for hPBSCs delivery to the respiratory airways in further clinical settings.

Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized stem cell niche. In highly innervated epithelium, peripheral nerves compose perineural niche and support stem cell homeostasis by releasing a variety of neurotransmitters, hormones, and growth factors and supplying trophic factors to the stem cells. Emerging evidence has shown that both sensory and motor nerves can regulate the fate of epithelial stem cells, thus influencing epithelium homeostasis. Understanding the mechanism of crosstalk between epithelial stem cells and neurons will reveal the important role of the perineural niche in physiological and pathological conditions. Herein, we review recent discoveries of the perineural niche in epithelium mainly in tissue homeostasis, with a limited touch in wound repair and pathogenesis.

Cell therapies could be the future of medicine. Many centers worldwide consider the use of stem cells to treat certain conditions. Well, proper homing remains the challenge, which means the ability to target the cells to the targeted site. Intraoperative transplantation of stem cells can overcome the homing challenge. However, it could be a double-edged sword, if a proper technique was not conducted. In this comment, a practical example of that is presented, where the use of stem cells in the vascular and neurovascular surgeries shows a promising potential, but the way in which the cells are processed and introduced is a critical step that should be given a lot of attention.

Background: The recent newly appeared Coronavirus disease (COVID-19), caused by an enveloped RNA virus named "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)", is associated with severe respiratory morbidity and mortality. Recent studies have shown that lymphopenia and a cytokine mass release represent important pathogenic features, with clinical evidence of dyspnea and hypoxemia, often leading to acute respiratory distress syndrome (ARDS), in severely ill patients, with a high death toll. Currently, stem cells are actively being investigated for their potential use in many "untreatable" diseases. In this regard and in particular, Mesenchymal Stem Cells (MSC), due to their intrinsic features, including either ability to impact on regulation of the immune system, or association with both anti-viral and anti-inflammatory properties, or potential for differentiation into several cell lineages, have become a promising tool for cell and molecular-based therapies. On this background, we wished to explore whether human umbilical cord-derived mesenchymal stem cells (hUCMS) would represent a potential viable therapeutic approach for the management of critically ill COVID19 patients.

Methods: We tested the hUCMS effects on peripheral blood mononuclear cell (PBMCs) retrieved from patients with COVID19 (Ethical Committee CEAS Umbria, Italy CER N°3658/20 7, May, 2020), both as free cell monolayers and after envelopment in sodium alginate microcapsules. Both cell systems, after priming with IFN-γ, proved able to produce several immunomodulatory molecules such as IDO1 and HLAG5, although only the microencapsulated hUCMS were associated with massive and dose-dependent production of these factors.

Results: The microencapsulated hUCMS improved allo-suppression in mixed lymphocytes reactions (MLRs), while also blunting T helper 1 and T helper 17 responses, that are involved with the cytokine storm and greatly contribute to the patient death. Moreover, we observed that both free and microencapsulated hUCMS permitted 5 days survival of in vitro culture maintained PBMCs extracted from very ill patients.

Conclusion: We have provided evidence that microencapsulated hUCMS in vitro, seem to represent a powerful tool to impact on several immune pathways, clearly deranged in COVID19 patients. Further study is necessary to begin in vivo assessment of this experimental system, upon determining both, the most appropriate time of the disease onset for intervention, and cell dosage/patient of our experimental product.