Background: Global population growth and population aging continue to accelerate, and lead to a further increase in the risk of neurological diseases worldwide. Extracellular vesicles secreted by mesenchymal stem cells carry many proteins, lipids, and genetic material that mediate cell-to-cell communication and improve therapeutic outcomes for neurological disorders. Stem cells from human exfoliated deciduous teeth are considered a suitable cell source for tissue regeneration, which exerts therapeutic effects via the secretion of exosomes.
Methods: This study was performed to assess the effect of functionalized exosomes on neural differentiation of embryonic carcinoma cell line P19. We stimulated stem cells from human exfoliated deciduous teeth with the glycogen synthase kinase-3β inhibitor TWS119 and then extracted its exosomes. P19 cells were induced to differentiate using functionalized exosomes, and the biological functions and involved signaling pathways of differentially expressed genes were analyzed by RNA-sequencing. Immunofluorescence techniques detected neuronal specific markers.
Results: It was found that TWS119 activated the Wnt signaling pathway in stem cells from human exfoliated deciduous teeth. RNA-sequencing showed that upregulated differentially expressed genes in the functionalized exosome-treated group were responsible for cell differentiation, neurofilament, and structural constituent of the synapse. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the functionalized exosome-treated group activated the Wnt signaling pathway. Immunofluorescence showed that functionalized exosomes induced neurite outgrowth in P19 cells.
Conclusion: Our results demonstrated that functionalized exosomes promoted neural differentiation of P19 cells by activating the Wnt signaling pathway.
Background: Dand5 encodes a protein that acts as an antagonist to Nodal/TGF-β and Wnt pathways. A mouse knockout (KO) model has shown that this molecule is associated with left-right asymmetry and cardiac development, with its depletion causing heterotaxia and cardiac hyperplasia.
Objective: This study aimed to investigate the molecular mechanisms affected by the depletion of Dand5.
Methods: DAND5-KO and wild-type embryoid bodies (EBs) were used to assess genetic expression with RNA sequencing. To complement the expression results that pointed towards differences in epithelial to mesenchymal transition (EMT), we evaluated migration and cell attachment. Lastly, in vivo valve development was investigated, as it was an established model of EMT.
Results: DAND5-KO EBs progress faster through differentiation. The differences in expression will lead to differences in the expression of genes involved with Notch and Wnt signalling pathways, as well as changes in the expression of genes encoding membrane proteins. Such changes were accompanied by lower migratory rates in DAND5-KO EBs, as well as higher concentrations of focal adhesions. Within valve development, Dand5 is expressed in the myocardium underlying future valve sites, and its depletion compromises correct valve structure.
Conclusion: The DAND5 range of action goes beyond early development. Its absence leads to significantly different expression patterns in vitro and defects in EMT and migration. These results have an in vivo translation in mouse heart valve development. Knowledge regarding the influence of DAND5 in EMT and cell transformation allows further understanding of its role in development, or even in some disease contexts, such as congenital heart defects.
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Stress urinary incontinence (SUI) is a common urinary system disease worldwide. Nowadays, medical therapy and surgery can control the symptoms and improve the life quality of patients. However, they might also bring about complications as the standard therapy fails to address the underlying problem of urethral sphincter dysfunction. Recent advances in cell technology have aroused interest in the use of autologous stem cell therapy to restore the ability of urinary control. The present study reviewed several types of stem cells for the treatment of SUI in the experimental and clinical stages.
Background: Intestinal disease is a common disease, which can cause serious digestion and absorption disorders, endanger the lives of patients and seriously affect the quality of life of people. Finding an effective treatment is a difficult problem at present, and stem cell therapy as a treatment has high application potential in intestinal-related diseases.
Purpose: This paper mainly summarizes the mechanism, research progress and future development trend of stem cells in the treatment of intestinal diseases in the past decade, hoping to provide a reference for future researchers in the research and application of stem cells and intestinal diseases.
Methods: Stem cells, inflammatory bowel diseases, Crohn's disease, radiation-induced intestinal injury, radiation enterocolitis, and extracellular vesicles were used as search terms. Relevant references in the past ten years were searched in CNKI journal full-text database, PubMed database, VIP network and Wanfang medical network, and 80 literature studies meeting the requirements were finally included for review.
Results: This paper summarizes the research and application of stem cells in intestinal diseases from 2012 to 2021, and expounds on the specific mechanism of stem cells in the treatment of intestinal diseases. It has been found that stem cells can treat intestinal injury or inflammation in different ways.
Conclusion: Future stem cells may also be used to reverse the natural aging of intestinal function, improve intestinal function, and strengthen gastrointestinal function.
Background: Over the past few years, mesenchymal stem cells (MSCs) have been regarded as effective for treating various diseases. Among the types of MSCs, human umbilical cord mesenchymal stem cells (hUC-MSCs) have been widely studied because of their advantages in non-invasive damage to donors and the wide range of sources.
Main body: This article reviews three aspects of hUC-MSCs. Foremost are the latest advances in the cultivation and preparation methods of hUC-MSCs. Furthermore, the treatments mechanism of hUCMSCs in organ transplantation and liver diseases. Finally, a summary of their use in clinical trials in liver diseases. The first part of this paper emphasizes the differences between the selection area and culture factors, including the separation method, long-term culturing in vitro, medium composition, serum, and three-dimensional (3D) skeleton system training, which could affect the characteristics of hUC-MSCs and the treatment of diseases. The second section mainly stresses the mechanisms of hUC-MSCs in the treatment of diseases, including immunoregulation and transdifferentiation into hepatocyte-like cells. Many new technologies mark and track cells in vivo and their safety. Briefly mention its role in the treatment of other diseases and vaccine preparation. In the third part, to accelerate the application of hUC-MSCs in the treatment of clinical diseases, it is necessary to expand the sample size of clinical trials to ensure their safety in the human body and determine the most effective infusion method and volume.
Conclusion: hUC-MSCs have a substantial potential to become a more effective treatment for liver diseases. Clinical trials and mechanisms have laid the foundation for the normalization of clinical hUC-MSCs delivery.
Intervertebral Disc Degeneration (IDD) is recognized as an aging process, an important and most common pathological condition caused by an imbalance of anabolic and catabolic metabolisms in the Intervertebral Disc (IVD), and leads to changes in the Extracellular Matrix (ECM), impaired metabolic regulation of Nucleus Pulposus (NP), and increased oxidative stress. IDD is mostly associated with pain in the back and neck, which is referred to as a type of disability. Pharmacological and surgical interventions are currently used to treat IDD, but evidence has shown that these interventions do not have the ability to inhibit the progression of IDD and restore IVD function because IVD lacks the intrinsic capacity for regeneration. Thus, therapies that rely on a degenerative cell repair mechanism may be a viable alternative strategy. Biological interventions have been assessed by attempting to regenerate IVD by restoring ECM and cellular function. Over the past decade, stem cell-based therapies have been considered, and promising results have been obtained in various studies. Given this, we reviewed clinical trials and preliminary studies of biological disc repair with a focus on stem cell therapy-based therapies.
Objective: The aim of the study was to reveal the changes in serum protein composition and content in macaques during the process of ageing, and explore the effect of bone marrow mesenchymal stem cell (BMMSC) on the serum protein expression profile in elderly macaques.
Methods: Naturally ageing macaques were assessed according to age. BMMSCs were intravenously infused into aged macaques. In addition, peripheral blood was collected to obtain serum for dataindependent acquisition (DIA) protein sequencing to identify aging-related indicators. One hundred eighty days after macaques received BMMSC treatment, haemoxylin and eosin (HE) staining was performed to observe the morphology and structure of aortic arches.
Results: Compared to infant and young control macaques, aged macaques showed erythema on the face, dry skin, reduced amounts of hair on the head and back, and paleness. Cultured BMMSCs from the 4th passage (P4 BMMSCs) were grown in accordance with standards used to culture mesenchymal stem cells. After BMMSC treatment, the assessed aortic arches showed no calcium salt deposition or cell necrosis, and the characteristics of the serum protein expression profile tended to be similar to that of the infant and young groups, with the expression of 41 proteins upregulated with age and that of 30 proteins downregulated with age but upregulated after BMMSC treatment. Moreover, we identified 44 significantly differentially expressed proteins between the aged model and treatment groups; 11 of the upregulated proteins were related to vascular ageing, neuronal ageing and haematopoiesis, and 33 of the downregulated proteins were associated with neuronal ageing, cardiovascular disease, and tumours. Interestingly, S100 expression in serum was significantly decreased, COMP expression was significantly increased, NKAP expression reappeared, and LCN2, CSF1R, CORO1C, CSTB and RSU-1 expression disappeared after BMMSC treatment.
Conclusion: BMMSCs can reverse ageing-related serum protein expression.
Bone tissue engineering (BTE) is based on the participation and combination of different biomaterials, cells, and bioactive molecules to generate biosynthetic grafts for bone regeneration. Electrospinning has been used to fabricate fibrous scaffolds, which provide nanoscale architecture comprising interconnecting pores, resembling the natural hierarchy of tissues and enabling the formation of artificial functional tissues. Electrospun fibers for BTE applications have been mostly produced from polymers (chitosan, alginate, polycaprolactone, polylactic acid) and bioceramics (hydroxyapatite). Stem cells are among the most prolific cell types employed in regenerative medicine owing to their self-renewal and differentiation capacity. Most importantly, bioactive molecules, such as synthetic drugs, growth factors, and phytocompounds, are consistently used to regulate cell behavior inducing differentiation towards the osteoblast lineage. An expanding body of literature has provided evidence that these electrospun fibers loaded with bioactive molecules support the differentiation of stem cells towards osteoblasts. Thus, this review briefly describes the current development of polymers and bioceramic-based electrospun fibers and the influence of bioactive molecules in these electrospun fibers on bone tissue regeneration.
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