Current stem cell research & therapy最新文献

Background: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis.

Aim: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis.

Methods: After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl₄ group (CCl₄), Fx group (CCl₄+Fx), PD-MSCs group (CCl₄+MSCs) and cotreatment group (CCl₄+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay.

Results: Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas.

Conclusion: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

Liver failure (LF) is serious liver damage caused by multiple factors, resulting in severe impairment or decompensation of liver synthesis, detoxification, metabolism, and biotransformation. The general prognosis of LF is poor with high mortality in non-transplant patients. The clinical treatments for LF are mainly internal medicine comprehensive care, artificial liver support system, and liver transplantation. However, none of the above treatment strategies can solve the problems of all liver failure patients and has its own limitations. Mesenchymal stem cells (MSCs) are a kind of stem cells with multidirectional differentiation potential and paracrine function, which play an important role in immune regulation and tissue regeneration. In recent years, MSCs have shown multiple advantages in the treatment of LF in pre-clinical experiments and clinical trials. In this work, we reviewed the biological characteristics of MSCs, the possible molecular mechanisms of MSCs in the treatment of liver failure, animal experiments, and clinical application, and also discussed the existing problems of MSCs in the treatment of liver failure.

Background: Retinal aging is one of the common public health problems caused by population aging and has become an important cause of acquired vision loss in adults. The aim of this study was to determine the role of human umbilical cord mesenchymal stem cells (hUCMSCs) in delaying retinal ganglion cell (RGC) aging and part of the network of molecular mechanisms involved.

Methods: A retinal ganglion cell senescence model was established in vitro and treated with UCMSC. Successful establishment of the senescence system was demonstrated using β- galactosidase staining. The ameliorative effect of MSC on senescence was demonstrated using CCK8 cell viability and Annexin V-PI apoptosis staining. The relevant targets of RGC, MSC, and senescence were mainly obtained by searching the GeneCards database. The protein interaction network among the relevant targets was constructed using the String database and Cytoscape, and 10 key target genes were calculated based on the MCC algorithm, based on which Gene ontologies (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed. Changes in relevant target genes were detected using real-time fluorescence quantitative PCR and the mechanism of action of UCMSC was determined by RNA interference.

Results: β-galactosidase staining showed that UCMSC significantly reduced the positive results of RGC. The retinal aging process was alleviated. The bioinformatics screen yielded 201 shared genes. 10 key genes were selected by the MCC algorithm, including vascular endothelial growth factor A (VEGFA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), albumin (ALB), interleukin- 6 (IL6), tumor necrosis factor (TNF), tumor protein P53 (TP53), insulin (INS), matrix metalloproteinase 9 (MMP9), epidermal growth factor (EGF), interleukin-1β (IL1B), and enrichment to related transferase activity and kinase activity regulated biological processes involved in oxidative stress and inflammation related pathways. In addition, PCR results showed that all the above molecules were altered in expression after UCMSC involvement.

Conclusion: This experiment demonstrated the role of UCMSC in delaying retinal ganglion cell senescence and further elucidated that UCMSC may be associated with the activation of VEGFA, TP53, ALB, GAPDH, IL6, IL1B, MMP9 genes and the inhibition of INS, EGF, and TNF in delaying retinal senescence.

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. Stem cell ability of self-renewal enables it to persist over time, thereby contributing to cancer relapse or recurrence and also resistance to current therapies. Therefore, targeting CSCs emerged as a promising strategy of cancer treatment. CSCs exhibit differentiation, self-renewal, and plasticity, they contribute to formation of malignant tumours, also favors, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Coventional cancer treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, eventually leading to relapse. This article focuses on the development of novel therapeutic strategies that combine conventional treatments and CSC inhibitors to eradicate cancer cells and CSCs, for the better and permanent treatment. However, the diversity of CSCs is a significant obstacle in the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

Background: Umbilical cord mesenchymal stem cells (UC-MSCs) are increasingly being utilized for immune-related disease therapies due to their low immunogenicity. However, the primary culture of UC-MSCs requires the supplementation of serum in the growth medium, which has posed a challenge due to ethical issues related to the collection method of the fetal bovine serum (FBS) that is routinely used in cell culture.

Aim: In order to address this, the purpose of this research was to assess the effectiveness of adult bovine serum (ABS) as a different and more affordable source of serum for the in-vitro cultivation of UC-MSCs. UC-MSCs were isolated from the umbilical cord of Wharton's jelly of cow immediately after birth, by digestion with Collagenase type I.

Method: ABS was collected from fresh bovine sources and heat-inactivated. The morphology of UC-MSCs was observed under an inverted microscope, and growth patterns, proliferative index, and doubling time were calculated every two days to compare the efficacy of ABS with FBS. Immunocytochemistry for specific markers was also conducted on the MSCs.

Result: The results showed a notable difference in morphology, growth rate, population doubling, and proliferative index between ABS and FBS.

Conclusion: Intriguingly, ABS proved to be an effective supplement in the growth medium for expanding UC-MSCs in vitro, providing a viable alternative to FBS.

Background: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has shown promising application prospects for its powerful immune regulation and tissue repair ability. Recent experimental data suggest that MSCs also regulate the composition of gut microbiota. The current review analyzed, for the first time, the research data linking MSCs and gut microbiota modulation in IBD models aiming at assessing the role of gut microbiota in MSCs repair of IBD.

Methods: A comprehensive and structured literature search was performed up to January 2023 on the PubMed, Web of Science, and Scopus databases. The quality and risk of bias assessment followed the PRISMA guidelines and SYRCLE's tool.

Results: A total of nine pre-clinical studies on animal models were included. Although the dose and route of MSCs applied were quite heterogeneous, results showed that MSCs displayed protective effects on intestinal inflammation, including mice general assessment, immunoregulation, and intestinal barrier integrity. Meanwhile, studies showed positive effects on the composition of gut flora with MSCs administration, which had been characterized by restoration of Firmicutes/ Bacteroides balance and reduction of Proteobacteria. The beneficial bacteria Akkermansia, Bifidobacterium, and Lactobacillus were also distinctly enriched, and the pathogenic bacteria Escherichia-Shigella was conversely decreased. The alpha and beta diversity were also regulated to resemble those of healthy mice. Microbial metabolic functions, such as biosynthesis of secondary bile acid and sphingolipid metabolism, and some biological behaviors related to cell regeneration were also up-regulated, while cancer function and poorly characterized cellular function were down-regulated.

Conclusion: Current data support the remodeling effect on gut microbiota with MSC administration, which provides a potential therapeutic mechanism for MSCs in the treatment of IBD. Additional studies in humans and animal models are warranted to further confirm the role of gut microflora in MSCs repairing IBD.

Backgrounds: Gastric cancer (GC) is threatening public health, with at least one million new cases reported each year. Rhomboid domain-containing protein 1 (RHBDD1) has been identified to regulate the proliferation, migration, and metastasis of cancer cells. However, the role of RHBDD1 in GC has not been elucidated.

Objects: This study aimed to investigate the role of RHBDD1 on the growth, metastasis, and stemness characteristics of GC.

Methods: RHBDD1 expression was analyzed from the TCGA databank. qRT-PCR was conducted to evaluate the transcription level of RHBDD1. Western blots were used to evaluate the protein expression of RHBDD1, CD133, CD44, Nanog, β-catenin and c-myc. Colony formation assay and transwell assay were conducted to evaluate the growth and metastasis of NCI-N87 cells, respectively. Sphere-forming assay was performed to study the stemness characteristics. The nude mice xenotransplantation model and immunohistochemistry (IHC) were performed to evaluate the growth of GC in vivo. Results: RHBDD1 expression is elevated in GC cells and clinical tissues. RHBDD1 expression is positively associated with cell proliferation and metastasis of GC cells. RHBDD1 knockdown suppresses the expression of CD133, CD44 and Nanog and attenuates sphere-forming ability. RHBDD1 activates the Wnt/β-catenin pathway via promoting the expression of β-catenin / c-myc and inducing β-catenin translocation into nuclear. RHBDD1 knockdown inhibits the growth of GC in nude mice xenotransplantation model.

Conclusion: RHBDD1 is highly expressed in GC, and its knockdown inhibits the growth, metastasis and stemness characteristics of GC cells through activating the Wnt/β-catenin pathway, suggesting that RHBDD1 has the potential to be a novel therapeutic target for GC treatment.

Wound infection often requires a long period of care and an onerous treatment process. Also, the rich environment makes the wound an ideal niche for microbial growth. Stable structures, like biofilm, and drug-resistant strains cause a delay in the healing process, which has become one of the important challenges in wound treatment. Many studies have focused on alternative methods to deal the wound infections. One of the novel and highly potential ways is mesenchymal stromal cells (MSCs). MSCs are mesoderm-derived pluripotent adult stem cells with the capacity for self-renewal, multidirectional differentiation, and immunological control. Also, MSCs have anti-inflammatory and antiapoptotic effects. MScs, as pluripotent stromal cells, differentiate into many mature cells. Also, MSCs produce antimicrobial compounds, such as antimicrobial peptides (AMP), as well as secrete immune modulators, which are two basic features considered in wound healing. Despite the advantages, preserving the structure and activity of MSCs is considered one of the most important points in the treatment. MSCs' antimicrobial effects on microorganisms involved in wound infection have been confirmed in various studies. In this review, we aimed to discuss the antimicrobial and therapeutic applications of MSCs in the infected wound healing processes.

Epigenetic regulation, including modifications of DNA, histone proteins and non-coding RNAs, play an important role in the regulation of gene expression and keep the heritable traits of progeny cells without changing DNA sequence. Recent years, epigenetic regulation of bone homeostasis are widely investigated and considered as a vital factor during the differentiation and function of osteoblasts, osteoclasts and osteocytes. Osteoporosis is a common degenerative bone disease which is characterized with decreased bone strength and increased risk of fracture. It has been testified that the abnormal bone metabolism homeostasis, especially in osteoclast function, take a fundamental role in osteoporosis pathogenesis. The reports between osteoporosis and epigenetic regulations are also increased gradually in recent years. In this review, we summarize the current developments of epigenetic regulation mechanism in bone development and remodeling, and emphasize the epigenetic features of osteoporosis and the potent therapy application of epigenetic drugs for osteoporosis.