The Role of the Notch Signaling Pathway in the Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells

Xing, Wanhong; Yang, Jianxin; Zheng, Ying; Yao, Lin; Peng, Xin; Chen, Yongqiang; Yang, Chao

doi:10.31083/j.fbl2902074

Cited by 4 publications

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Revolutionizing medicine: recent developments and future prospects in stem-cell therapy

Hussen,

Taheri,

Yashooa

et al. 2024

International Journal of Surgery

View full text Add to dashboard Cite

Stem-cell therapy is a revolutionary frontier in modern medicine, offering enormous capacity to transform the treatment landscape of numerous debilitating illnesses and injuries. This review examines the revolutionary frontier of treatments utilizing stem cells, highlighting the distinctive abilities of stem cells to undergo regeneration and specialized cell differentiation into a wide variety of phenotypes. This paper aims to guide researchers, physicians, and stakeholders through the intricate terrain of stem-cell therapy, examining the processes, applications, and challenges inherent in utilizing stem cells across diverse medical disciplines. The historical journey from foundational contributions in the late 19th and early 20th centuries to recent breakthroughs, including ESC isolation and iPSC discovery, has set the stage for monumental leaps in medical science. Stem cells’ regenerative potential spans embryonic, adult, induced pluripotent, and perinatal stages, offering unprecedented therapeutic opportunities in cancer, neurodegenerative disorders, cardiovascular ailments, spinal cord injuries, diabetes, and tissue damage. However, difficulties, such as immunological rejection, tumorigenesis, and precise manipulation of stem-cell behavior, necessitate comprehensive exploration and innovative solutions. This manuscript summarizes recent biotechnological advancements, critical trial evaluations, and emerging technologies, providing a nuanced understanding of the triumphs, difficulties, and future trajectories in stem cell-based regenerative medicine. Future directions, including precision medicine integration, immune modulation strategies, advancements in gene-editing technologies, and bioengineering synergy, offer a roadmap in stem cell treatment. The focus on stem-cell therapy’s potential highlights its significant influence on contemporary medicine and points to a future in which individualized regenerative therapies will alleviate various medical disorders.

show abstract

Revolutionizing medicine: recent developments and future prospects in stem-cell therapy

Hussen,

Taheri,

Yashooa

et al. 2024

International Journal of Surgery

View full text Add to dashboard Cite

show abstract

Cell Sheets Formation Enhances Therapeutic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Spinal Cord Injury

Zhao,

Wu,

Zhou

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

BackgroundIn recent years, the utilization of stem cell therapy and cell sheet technology has emerged as a promising approach for addressing spinal cord injury (SCI). However, the most appropriate cell type and mechanism of action remain unclear at this time. This study sought to develop an SCI rat model and evaluate the therapeutic effects of human umbilical cord mesenchymal stem cell (hUC‐MSC) sheets in this model. Furthermore, the mechanisms underlying the vascular repair effect of hUC‐MSC sheets following SCI were investigated.MethodsA temperature‐responsive cell culture method was employed for the preparation of hUC‐MSC sheets. The extracellular matrix (ECM) produced by hUC‐MSCs serves two distinct yet interrelated purposes. Firstly, it acts as a biologically active scaffold for transplanted cells, facilitating their attachment and proliferation. Secondly, it provides mechanical support and bridges spinal cord stumps, thereby facilitating the restoration of spinal cord function. The formation of the cavity within the spinal cord was evaluated using the Hematoxylin and Eosin (H&E) staining method. Subsequently, endothelial cells were cultivated with the conditioned medium (CM) obtained from hUC‐MSCs or hUC‐MSC sheets. The pro‐angiogenic impact of the conditioned medium of hUC‐MSCs (MSC‐CM) and the conditioned medium of hUC‐MSC sheets (CS‐CM) was evaluated through the utilization of the CCK‐8 assay, endothelial wound healing assay, and tube formation assay in an in vitro context. The development of glial scars, blood vessels, neurons, and axons in hUC‐MSCs and hUC‐MSC sheets was assessed through immunofluorescence staining.ResultsIn comparison to hUC‐MSCs, hUC‐MSC sheets demonstrated a more pronounced capacity to facilitate vascular formation and induce the regeneration of newborn neurons at the SCI site, while also reducing glial scar formation and significantly enhancing motor function in SCI rats. Notably, under identical conditions, the formation of cell sheets has been associated with a paracrine increase in the ability of the cells themselves to secrete pro‐angiogenic growth factors. During the course of the experiment, it was observed that the secretion of uPAR was the most pronounced among the pro‐angiogenic factors present in MSC‐CM and CS‐CM. This finding was subsequently corroborated in subsequent experiments, wherein uPAR was demonstrated to promote angiogenesis via the PI3K/Akt signaling pathway.ConclusionThe creation of cell sheets not only significantly enhances the biological function of hUC‐MSCs but also effectively retains the cells locally in spinal cord injury. Therefore, the transplantation of hUC‐MSC sheets can maximize the function of hUC‐MSCs, greatly reducing glial scar formation, enhancing vascular formation, and promoting the regeneration of neurons and axons. Additionally, the research findings prove that hUC‐MSC sheets activate the PI3K/Akt signaling pathway through uPAR secretion to enhance angiogenesis. The transfer of the entire extracellular matrix by hUC‐MSC sheets, in the absence of the introduction of additional exogenous or synthetic biomaterials, serves to further augment their potential for clinical application.

show abstract

Comprehensive analysis of NOTCH pathway with tumor environment in pancreatic adenocarcinoma

Wang,

Yin,

Chen

et al. 2024

Oncologie

View full text Add to dashboard Cite

Objectives Pancreatic adenocarcinoma (PAAD) ranks among the most prevalent malignant neoplasms, and multiple pathways are involved in its pathogenesis, including the NOTCH pathway. However, the variable biological functions of the pathway in PAAD are controversial. Methods RNA-seq data for PAAD was analyzed using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Utilizing Kaplan-Meier survival curves and Cox regression analyses, we examined the prognostic significance. The tumor microenvironment and immunotherapy responses were investigated using ssGSEA, ESTIMATE, and TIDE models. Functional enrichment analysis was used to explore gene functions. Results We identified NOTCH2, JAG1, NOTCH4, and DLL3 as high-priority members of the NOTCH pathway that modulates PAAD. Elevated NOTCH2 and JAG1 levels were markedly linked to reduced overall survival (OS), while increased NOTCH4 and DLL3 levels were significantly related to extended OS. Immune analyses showed that NOTCH-based scores were closely related to the immune microenvironment. NOTCH scores were not only closely correlated with tumor-infiltrating immune cells, but also with immunologically activated and immune checkpoint gene expression. The high NOTCH score group had a higher proportion of tumor-infiltrating immune cells and had better responses to immune checkpoint inhibitor therapy. Conclusions These data indicate that NOTCH2, JAG1, NOTCH4, and DLL3 could function as efficient prognostic biomarkers and therapeutic targets in PAAD, and patients with a high NOTCH score may have a significant response to immune checkpoint inhibitor treatment.

show abstract

The Role of the Notch Signaling Pathway in the Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells

Cited by 4 publications

References 128 publications

Revolutionizing medicine: recent developments and future prospects in stem-cell therapy

Revolutionizing medicine: recent developments and future prospects in stem-cell therapy

Cell Sheets Formation Enhances Therapeutic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Spinal Cord Injury

Comprehensive analysis of NOTCH pathway with tumor environment in pancreatic adenocarcinoma

Contact Info

Product

Resources

About