Stem Cell Reviews and Reports最新文献

The Cellular Heat Shock Response and in particular heat shock protein activation are vital stress reactions observed in both healthy and cancer cells. Hyperthermia (HT) has been proposed for several years as an advancing non-invasive cancer therapy. It selectively targets cancer cells through mechanisms influenced by temperature and temperature variations. This article delves into the impact of HT on cancer cells, especially cancer stem cells (CSCs), essential contributors to cancer recurrence and metastasis. HT has shown promise in eliminating CSCs, sensitizing them to conventional treatments and modulating the tumor microenvironment. The exploration extends to mesenchymal stem cells (MSCs), which exhibit both pro-tumorigenic and anti-tumorigenic effects. HT's potential in recruiting therapeutic MSCs for targeted delivery of antitumoral agents is also discussed. Furthermore, the article introduces Brain Thermodynamics-guided Hyperthermia (BTGH) technology, a breakthrough in temperature control and modulation of heat transfer under different conditions. This non-invasive method leverages the brain-eyelid thermal tunnel (BTT) to monitor and regulate internal brain temperature. BTGH technology, with its precision and noninvasive continuous monitoring capabilities, is under clinical investigation for applications in neurological disorders and cancer. The innovative three-phase approach involves whole-body HT, targeted brain HT, and organ-specific HT. In conclusion, the exploration of localized or whole-body HT offers promising avenues for cancer, psychiatric and neurological diseases. The ongoing clinical investigations and potential applications underscore the significance of understanding and harnessing heat's responses to enhance human health.

The aim of this study was to analyze the impact of human umbilical cord-derived MSCs (hUC-MSCs) on motor function in children with cerebral palsy (CP). The study enrolled 152 children with CP who received up to two courses of five hUC-MSCs injections. Children's motor functions were assessed with the Gross Motor Function Measure (GMFM), 6-Minute Walk Test (6-MWT), Timed Up and Go test (Up&Go test), and Lovett's test, and mental abilities were assessed with the Clinical Global Impression (CGI) scale. Data collected at visit 1 (baseline) and visit 5 (after four injections) were analyzed retrospectively. After four hUC-MSCs administrations, all evaluated parameters improved. The change in GMFM score, by a median of 1.9 points (IQR: 0.0-8.0), correlated with age. This change was observed in all GFMCS groups and was noticed in all assessed GMFM areas. A median increase of 75 m (IQR: 20.0-115.0) was noted on the 6-MWT, and this correlated with GMFM score change. Time on the Up&Go test was reduced by a median of 2 s (IQR: -3 to - 1) and the change correlated with age, GMFM score at baseline, and the difference observed on the 6-MWT. Results of Lovett's test indicated slight changes in muscle strength. According to the CGI, 75.5% (96/151) of children were seriously (level VI) or significantly ill (level V) at the 1^st visit, with any improvement observed in 63.6% (96/151) of patients at the 5^th visit, 23.8% (36/151) with improvement (level II) or great improvement (level I). In conclusion, the application of hUC-MSCs generally enhanced functional performance, but individual responses varied. The therapy also benefited children with high level of disability but not to the same extent as the initially less disabled children. Although younger patients responded better to the treatment, older children can also benefit. Trial Registration 152/2018/KB/VII and 119/2021/KB/VIII. Retrospective registration in ClinicalTrials: ongoing.

Although stem/progenitor cell therapy shows potential for myocardial infarction repair, enhancing the therapeutic efficacy could be achieved through additional genetic modifications. HCLS1-associated protein X-1 (HAX1) has been identified as a versatile modulator responsible for cardio-protective signaling, while its role in regulating stem cell survival and functionality remains unknown. In this study, we investigated whether HAX1 can augment the protective potential of Sca1⁺ cardiac stromal cells (CSCs) for myocardial injury. The overexpression of HAX1 significantly increased cell proliferation and conferred enhanced resistance to hypoxia-induced cell death in CSCs. Mechanistically, HAX1 can interact with Mst1 (a prominent conductor of Hippo signal transduction) and inhibit its kinase activity for protein phosphorylation. This inhibition led to enhanced nuclear translocation of Yes-associated protein (YAP) and activation of downstream therapeutic-related genes. Notably, HAX1 overexpression significantly increased the pro-angiogenic potential of CSCs, as demonstrated by elevated expression of vascular endothelial growth factors. Importantly, implantation of HAX1-overexpressing CSCs promoted neovascularization, protected against functional deterioration, and ameliorated cardiac fibrosis in ischemic mouse hearts. In conclusion, HAX1 emerges as a valuable and efficient inducer for enhancing the effectiveness of cardiac stem or progenitor cell therapeutics.

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). The SARS-CoV-2 pandemic has unveiled complex pathophysiological mechanisms underpinning COVID-19, notably inducing a systemic acquired vascular hemopathy characterized by endothelial dysfunction and intussusceptive angiogenesis, a rapid vascular remodeling process identified as a hallmark in severe COVID-19 cases affecting pulmonary and cardiac tissues. Stem cell migration have been proposed as significant regulators of this neoangiogenic process. In a monocentric cross-sectional study, through spectral flow cytometry analysis of peripheral blood mononuclear cells, we identified a distinct stem cell subpopulation mobilized in critical COVID-19. Indeed, by an unsupervised analysis generating a UMAP representation we highlighted eleven different clusters in critical and non-critical COVID-19 patients. Only one cluster was significantly associated to critical COVID-19 compared to non-critical patients. This cluster expressed the markers: CD45dim, CD34+, CD117+, CD147+, and CD143+, and were negative for CD133. Higher level of expression of hemangioblast markers CD143 were found in critical COVID-19 patients. This population, indicative of hemangioblast-like cells, suggests a key role in COVID-19-related neoangiogenesis, potentially driving the severe vascular complications observed. Our findings underscore the need for further investigation into the contributions of adult stem cells in COVID-19 pathology, offering new insights into therapeutic targets and interventions.

Mesenchymal stem cells (MSCs) are extensively researched for therapeutic applications in tissue engineering and show significant potential for clinical use. Intrinsic or extrinsic factors causing senescence may lead to reduced proliferation, aberrant differentiation, weakened immunoregulation, and increased inflammation, ultimately limiting the potential of MSCs. It is crucial to comprehend the molecular pathways and internal processes responsible for the decline in MSC function due to senescence in order to devise innovative approaches for rejuvenating senescent MSCs and enhancing MSC treatment. We investigate the main molecular processes involved in senescence, aiming to provide a thorough understanding of senescence-related issues in MSCs. Additionally, we analyze the most recent advancements in cutting-edge approaches to combat MSC senescence based on current research. We are curious whether the aging process of stem cells results in a permanent "memory" and if cellular reprogramming may potentially revert the aging epigenome to a more youthful state.

Background: Sepsis is a life-threatening disorder with no definitive cure. Preclinical studies suggest that extracellular vesicles derived from mesenchymal stromal cells (EV-MSCs) can mitigate inflammatory conditions, potentially leading to increased survival and reduced organ dysfunction during sepsis. Our aim to conduct this systematic review and meta-analysis is assessing the EV-MSCs therapeutic efficacy in sepsis.

Methods: PubMed, Embase, Scopus, WOS and ProQuest databases and also Google Scholar search engine were searched for published articles. We used hazard ratio (HR) and standardized mean difference (SMD) as effect sizes to evaluate the therapeutic effect of EV-MSCs on survival rate and determine their effect on reducing organ dysfunction, respectively. Finally, we employed GRADE tool for preclinical animal studies to evaluate certainty of the evidence.

Results: 30 studies met the inclusion criteria for our article. Our meta-analysis results demonstrate that animals treated with MSC-EVs have better survival rate than untreated animals (HR = 0.33; 95% CI: 0.27-0.41). Our meta-analysis suggests that EV-MSCs can reduce organ dysfunctions in sepsis, such as the lung, kidney, and liver. Additionally, EV-MSCs decrease pro-inflammatory mediators like TNF-α, IL-1β, and IL-6.

Conclusion: Our results indicate that EV-MSCs can be as promising therapy for sepsis management in animal models and leading to increased survival rate and reduced organ dysfunction. Furthermore, our study introduces a novel tool for risk of bias assessment and provides recommendations based on various analysis. Future studies with aiming to guide clinical translation can utilize the results of this article to establish stronger evidence for EV-MSC effectiveness.

Cell surface marker expression is one of the criteria for defining human mesenchymal stem or stromal cells (MSC) in vitro. However, it is unclear if expression of markers including CD73 and CD90 reflects the in vivo origin of cultured cells. We evaluated expression of 15 putative MSC markers in primary cultured cells from periosteum and cartilage to determine whether expression of these markers reflects either the differentiation state of cultured cells or the self-renewal of in vivo populations. Cultured cells had universal and consistent expression of various putative stem cell markers including > 95% expression CD73, CD90 and PDPN in both periosteal and cartilage cultures. Altering the culture surface with extracellular matrix coatings had minimal effect on cell surface marker expression. Osteogenic differentiation led to loss of CD106 and CD146 expression, however CD73 and CD90 were retained in > 90% of cells. We sorted freshly isolated periosteal populations capable of CFU-F formation on the basis of CD90 expression in combination with CD34, CD73 and CD26. All primary cultures universally expressed CD73 and CD90 and lacked CD34, irrespective of the expression of these markers ex vivo indicating phenotypic convergence in vitro. We conclude that markers including CD73 and CD90 are acquired in vitro in most 'mesenchymal' cells capable of expansion. Overall, we demonstrate that in vitro expression of many cell surface markers in plastic-adherent cultures is unrelated to their expression prior to culture.

The placenta plays a crucial role in maintaining normal pregnancy. The failure of spiral artery remodeling (SAR) is a key factor leading to placental ischemia and poor perfusion which is strongly associated with obstetric diseases, including preeclampsia (PE) and fetal growth restriction (FGR). Existing interventions for PE and FGR are limited and termination of pregnancy is inevitable when the maternal or fetus condition deteriorates. Considering the safety of the mother and fetus, treatments that may penetrate the placental barrier and harm the fetus are not accepted. Developing targeted treatment strategies for these conditions is urgent and necessary. With the proven efficacy of targeted therapy in treating conditions such as endometrial cancer and trophoblastic tumors, research on placental dysfunction continues to deepen. This article reviews the studies on placenta-targeted treatment and drug delivery strategies, summarizes the characteristics proposes corresponding improvement measures in targeted treatment, provides solutions for existing problems, and makes suggestions for future studies.

Non-coding RNA has many types which has rich functions and plays an important role in the study of basic molecular mechanisms. Many non-coding RNA have important implications for pluripotent stem cells and embryonic stem cells. It has been found to affect the self-renewal and osteogenesis of many types of stem cells. They have also been found to regulate stem cell proliferation and induct bone differentiation. Periodontal ligament stem cells are essential for the regeneration of periodontal tissue. In recent years, in the field of stomatology, studies have found that many non-coding RNA also have significant regulatory effects on the proliferation and differentiation of periodontal stem cells and may become potential therapeutic targets for many common periodontal diseases such as periodontitis, bone/tooth/soft tissue loss and orthodontic treatment. Therefore, we summarized the current research status of non-coding RNA in the field of molecular mechanism of periodontal ligament stem cells and prospected its future progress.

Background: Pathogenesis and malignant potential of Oral submucous fibrosis(OSMF) have always been a topic of interest among the researchers. Despite OSMF being a collagen metabolic disorder, the alterations occurring in the connective tissue stroma affects the atrophic surface epithelium in later stages and progresses to malignant phenotypes. The present review aims to summarize the role of stem cells in the pathogenesis and malignant transformation of oral submucous fibrosis.

Materials and methods: A literature search was carried out using data banks like Medline and Embase, google scholar and manual method with no time frame, pertinent to the role of mucosal stem cells in OSMF and its malignisation. The relevant literature was reviewed, critically appraised by all the authors and compiled in this narrative review.

Results: Critical appraisal and evaluation of the data extracted from the selected articles were compiled in this review. The collated results highlighted the upregulation and downregulation of various stem cell markers during the progression and malignisation of OSMF were depicted in a descriptive and detail manner in the present review.

Conclusion: We highlight the potential of mucosal stem cells in the regulation and malignisation of OSMF. However, future large-scale clinical studies will be needed to support whether manipulation of this stem cells at molecular level will be sufficient for the treatment and preventing the malignant transformation of OSMF.