Current stem cell research & therapy最新文献

Background: Cancer stem cells (CSC) play an important role in the development of Liver Hepatocellular Carcinoma (LIHC). However, the regulatory mechanisms between acetylation- associated genes (HAGs) and liver cancer stem cells remain unclear.

Objective: To identify a set of histone acetylation genes (HAGs) with close associations to liver cancer stem cells (LCSCs), and to construct a prognostic model that facilitates more accurate prognosis assessments for LIHC patients.

Methods: LIHC expression data were downloaded from the public databases. Using mRNA expression- based stemness indices (mRNAsi) inferred by One-Class Logistic Regression (OCLR), Differentially Expressed Genes (DEGs) (mRNAsi-High VS. mRNAsi-Low groups) were intersected with DEGs (LIHC VS. normal samples), as well as histone acetylation-associated genes (HAGs), to obtain mRNAsi-HAGs. A risk model was constructed employing the prognostic genes, which were acquired through univariate Cox and Least Shrinkage and Selection Operator (LASSO) regression analyses. Subsequently, independent prognostic factors were identified via univariate and multivariate Cox regression analyses and then a nomogram for prediction of LIHC survival was developed. Additionally, immune infiltration and drug sensitivity analysis were performed to explore the relationships between prognostic genes and immune cells. Finally, the expressions of selected mRNAsi-HAGs were validated in the LIHC tumor sphere by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) assay and western blot analysis.

Results: Among 13 identified mRNAsi-HAGs, 3 prognostic genes (HDAC1, HDAC11, and HAT1) were selected to construct a risk model (mRNAsi-HAGs risk score = 0.02 * HDAC1 + 0.09 * HAT1 + 0.05 * HDAC11). T-stage, mRNAsi, and mRNAsi-HAGs risk scores were identified as independent prognostic factors to construct the nomogram, which was proved to predict the survival probability of LIHC patients effectively. We subsequently observed strongly positive correlations between mRNAsi-HAGs risk score and tumor-infiltrating T cells, B cells and macrophages/monocytes. Moreover, we found 8 drugs (Mitomycin C, IPA 3, FTI 277, Bleomycin, Tipifarnib, GSK 650394, AICAR and EHT 1864) had significant correlations with mRNAsi-HAGs risk scores. The expression of HDAC1 and HDAC11 was higher in CSC-like cells in the tumor sphere.

Conclusion: This study constructed a mRNAsi and HAGs-related prognostic model, which has implications for potential immunotherapy and drug treatment of LIHC.

Background: With the passage of time, the incidence rate of diabetes continues to rise. As a common and serious complication of diabetes, the economic burden of diabetes ulcers is also increasing. However, there is currently no unified clinical treatment strategy for its repair and research, and the treatment effect is not satisfactory. Exosomes derived from MSCs play a crucial role in improving diseases.

Methods: This study used the explant culture method to isolate human umbilical cord mesenchymal stem cells (hucMSCs) from Wharton's jelly, which were identified by flow cytometry and differentiation potential and evaluated tumorigenic potential. The supernatant of P3-P5 cell culture medium was collected and high-concentration human umbilical cord mesenchymal stem cell exosomes (hucMSCs-Exos) were isolated through ultracentrifugation. Qualitatively identified were finished by transmission electron microscopy (TEM), nanosight tracking analysis (NTA) and Western blot (WB). CCK-8 assay and cell scratch experiment were used to evaluate the effects of hucMSCs-Exos on proliferation and migration ability of cells; chicken embryo chorioallantoic membrane experiment (CAM) was used to evaluate the angiogenic effect of hucMSCs-Exos. In order to study the effect of hucMSCs-Exos on diabetes wound healing, type 2 diabetes mellitus (T2DM) mouse model was constructed by a high-fat feeding and a low-dose streptozotocin (STZ) injection. Fasting blood glucose and blood lipids were measured and oral glucose tolerance test (OGTT) was conducted; HucMSCs- Exos were subcutaneously injected into the T2DM wound model mice which were established by a high-fat diet and by a low-dose STZ, and the wound healing was evaluations.

Results: Cells were isolated by explant culture method, and flow cytometry analyses showed that these isolated cells were positive for cells markers CD29, CD90, and CD105, while negative for CD34 and CD45; moreover, these cells could be induced to osteoblasts, adipocytes, and islet-like cells. The tumorigenic experiments showed that these cells have no tumorigenicity. HucMSCs-Exos, separated by ultracentrifugation, displayed spherical or ellipsoidal vesicles with a diameter of around 120 nm, positive for CD9, CD63, and CD81. And they could promote cell proliferation and migration, as well as promote vascular growth (p < 0.01). In vivo experiments showed that hucMSCs-Exos had a promoting effect on wound repair in T2DM mice (p < 0.01).

Conclusion: This study provides a new scheme for the treatment of T2DM ulcer.

Background: Alcohol-induced fatty liver disease (AFLD) begins with steatosis and may progress to a range of pathological liver changes, including fibrosis, cirrhosis, and complications. Menstrual blood-derived endometrial stem cells (MenSCs) have shown potential therapeutic effects against various types of liver damage. However, the liver-protective effects of MenSCs in AFLD are not well understood. This study aimed to evaluate the therapeutic effects of MenSCs on AFLD progression.

Methods: MenSCs were sourced from women in good health (N=5, 25-34 years old). Male C57BL/6 mice were separated into three distinct groups to establish the mouse models. The AH/- MenSCs group received MenSCs (5×10⁵ cells/mouse) transplantation through tail injection on the 7th and 13th days following the initiation of the alcohol-induced fatty liver model. The therapeutic effects of MenSCs transplantation in AFLD mouse models were subsequently explored using qPCR, Western blotting, histopathological examination, and mRNA sequencing analysis.

Results: MenSCs significantly improved liver function and reduced lipid accumulation in AFLD. Treatment with MenSCs was also found to reduce the expression levels of inflammatory cytokines and profibrotic markers in the liver tissues of the mouse model. Additionally, the MenSCs- treated group demonstrated a significant reduction in endoplasmic reticulum (ER) stress and oxidative stress, along with an increase in autophagic activity.

Conclusion: The findings provided preliminary evidence of the multifaced protective effects of MenSCs in AFLD.

Objectives: This study aims to explore the therapeutic potential of mesenchymal stem cells (MSC) in treating diabetic nephropathy (DN) by investigating their effect on IL-11 modulation in a mouse model.

Methods: The effects of MSC therapy on DN were examined both in vivo and in vitro. Sixty adult male C57BL/6 mice were divided into the streptozotocin (STZ) diabetes (T1D) and the high-fat diet diabetes (T2D) models, with both groups receiving MSC treatment or saline for 4 or 8 weeks. Blood glucose, serum urea, interleukin-11 (IL-11), and kidney fibrosis markers were measured. Additionally, western blotting was used to assess levels of Type I and III collagen, E-Cadherin, α- smooth muscle actin (α-SMA), Vimentin, and ferroptosis suppressor protein 1 (FSP-1).

Results: MSC-treated T1D and T2D mice showed reduced blood glucose, serum urea, IL-11, TGF-β, and fibrosis markers (type I and III collagen, α-SMA, Vimentin, FSP-1), alongside increased E-Cadherin expression. Similar effects were observed in vitro using mouse glomerular epithelial cells, confirming MSC-mediated suppression of fibrosis pathways.

Conclusion: MSC therapy improves nephropathy, likely by inhibiting IL-11 and reducing fibrosis- related markers, making it a promising treatment for DN.

Introduction: Human menstrual blood stem cells (huMenSCs) appear to be pre-clinically safe but a controlled phase I clinical trial is required to determine safety for clinical applications.

Methods: HuMenSCs established from healthy donors were free of bacteria, mycoplasma, chlamydia, and endotoxin. P3 (passage 3) huMenSCs expressed the mesenchymal stem cell markers. P6 huMenSCs were developmental multipotential and could translocated into the uterine subepithelial stroma after intrauterine transplantation. After 10 and 15 passages, the huMenSCs kept normal karyotypes.

Results: Gene expression showed that compared with the human umbilical cords mesenchymal stem cells (huMSCs), the huMenSCs affected the stromal cells more effectively. The huMenSCs possibly enhanced the stromal cell multiplication and "decidualization" process initiated by Igfbp1.

Conclusion: Expression of Igfbp1, Atf3, Ptgs2, Hoxa10, Nr4a1, and Fox A2 were significantly increased in the stromal cells of the huMenSCs transplanted uterine.

Objectives: Diabetic foot (DF) poses a great challenge to us due to its poor therapeutic effect. To seek a new cure, the human dental pulp mesenchymal stem cells (hDP-MSCs) were modified by vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) (hEDP-MSCs) to investigate their curative effect on DF wound in animal models.

Methods: Forty-eight rats with DF constructed with streptozotocin and ligation of femoral arteries, were randomly divided into six equal groups, which respectively received an intramuscular injection of normal saline (Control group), hDP-MSCs, VEGFA-modified hDP-MSCs, bFGFmodified hDP-MSCs, hEDP-MSCs, and Ad.VEGF.FGF (Ad.FV). The tissues around DF wound were collected to investigate the level of CD31, alpha-smooth muscle actin (α-SMA), and cytokines. The expression of Notch1, Hes1, and CD105 were assessed via Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) after administration.

Results: The hEDP-MSCs increased capillaries and decreased wound area (%). QRT-PCR showed that hEDP-MSCs over-expressed the mRNA of Notch1, hairy and enhancer of split 1 and CD105 in peri-wound tissue post-treatment. Meanwhile, the hEDP-MSCs expressed more CD31 and α-SMA than other groups. The hEDP-MSCs expressed more VEGFA and bFGF than hDP-MSCs, and yet less than Ad.FV. Compared with hDP-MSCs, the hEDP-MSCs down-regulated the expressions of interleukin-1 beta (IL-1β), interleukin (IL-6), and tissue necrosis factor α (TNF-a) post-treatment.

Conclusion: This study highlights the curative effect of hEDP-MSCs in the wound healing process, and demonstrates the decisive function of hEDP-MSCs in promoting angiogenesis and reducing inflammation.

Tendinopathy is a prevalent and debilitating musculoskeletal disorder. Uncertainty remains regarding its pathophysiology, but it is believed to be a combination of inflammation, damage, degenerative changes, and unsuccessful repair mechanisms. Cell-based therapy is an emerging regenerative medicine modality that uses mesenchymal stem cells (MSCs), their progeny or exosomes to promote tendon healing and regeneration. It is based on the fact that MSCs can be differentiated into tenocytes, the major cell type within tendons, and facilitate tendon repair. Photobiomodulation (PBM) is a non-invasive and potentially promising therapeutic technique that utilizes low-level light to alter intracellular processes and promote tissue healing and regeneration. Recent studies have examined the potential for PBM to improve MSC therapy use in tendinopathy by promoting viability, proliferation, and differentiation. As well as enhance tendon regeneration. This review focuses on Photobiomodulation and MSC therapy applications in regenerative medicine and their potential for tendon tissue engineering.

Objective: While clinical trials exploring stem cells for regenerating periodontal tissues have demonstrated positive results, there is a limited availability of systematic literature reviews on this subject. To gain a more comprehensive understanding of stem cell interventions in periodontal regeneration, this meta-analysis is undertaken to assess the beneficial effects of stem cells in human periodontal regeneration.

Methods: "PubMed," "PubMed Central," "Web of Science," "Embase Scopus" "Wanfang," and "CNKI," were used to extract clinical studies related to the utilization of stem cells in repairing periodontal tissue defects. This search included studies published up until October 5, 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell-free therapy for regenerating periodontal tissues. Meta-analysis was conducted using Review Manager software (version 5.4).

Results: This meta-analysis synthesized findings from 15 selected studies investigating the impact of stem cell interventions on periodontal tissue regeneration. The "stem cell" group displayed a substantial reduction in clinical attachment level (CAL) compared to the "control" group within 3 to 12 months post-surgery. However, no significant differences in CAL gain were found between groups. Probing pocket depth (PPD) significantly decreased in the "stem cell" group compared to the "control" group, particularly for follow-up periods exceeding 6 months, and dental stem cell treatment exhibited notable improvements. Conversely, no significant differences were observed in PPD reduction. Gingival recession (GR) significantly decreased in the "stem cell" group compared to the "control" group at 3 to 12 months post-surgery. No significant differences were observed in GR reduction between groups. No significant differences were identified in cementoenamel junction-bone distance reduction, infrabony defect reduction, or bone mineral density increase between the two groups. Furthermore, no significant changes were observed in the gingival index, plaque index, or width of keratinized gingiva.

Conclusion: In conclusion, while stem cell-based therapy offers promising prospects for periodontal defect treatment, there are notable limitations in the current body of research. Larger, multicenter, double-blind RCTs with robust methodologies are needed to provide more reliable evidence for stem cell-based intervention in periodontitis.

Background: Premature Ovarian Failure (POI), a prevalent gynecological, endocrine disease, significantly impairs the reproductive health of women of childbearing age and presents a formidable challenge to clinicians. Until now, there has been a lack of effective treatments to fundamentally improve ovarian function in patients with POI. Stem cell therapy has emerged as a promising treatment in the field of POI, with notable research progress achieved to date.

Objectives: This review sought to analyze the current status and hotspots of research on stem cell therapy for POI, forecasting future directions through bibliometrics.

Methods: Research related to stem cell therapy for POI from 2000 to 2023 was searched in the Web of Science Core Collection (WOSCC) database by setting subject-term, and the literature was analyzed econometrically using VOSviewer, CiteSpace, and the R package "bibliometrix."

Results: According to our search and screening strategy, 203 pieces of literature related to stem cell therapy for POI were obtained and analyzed. There is a marked annual increase in publications, with a particularly rapid ascent in recent years. China has become the most prolific country in this field, with 136 publications. Shanghai Jiao Tong University ranked first among many universities and institutions in terms of the number of publications and citations. Stem Cell Research & Therapy was the most popular and influential journal in the field of stem cell therapy for POI. Lai Dongmei has published the most papers, while Liu Te boasts the highest frequency of co-citations. Investigation into the mechanisms of exosomes derived from stem cells and their associated signaling pathways is anticipated to be a crucial research topic in stem cell therapy for POI.

Conclusion: This review offers the first comprehensive and systematic analysis of the field of stem cell therapy for POI, with a visual representation of the findings. By summarizing the current status and projecting forthcoming trends, this study aims to offer guidance and a reference for scholars in the field.

Vascular stents and stem cells have been used in high-acuity cases for many decades, particularly in cardiology. Providing the physician with another avenue of treatment, they have had a reasonable amount of success. However, there has been very little research conducted on seeding vascular stents with stem cells when treating intracranial aneurysms. Our work aims to understand the current literature available on the viability of such stents and the future directions one should take when choosing stents seeded with stem cells. Three computerized searches in PubMed were used. Four papers met the criteria, and two were excluded. There have been some experiments where the efficacy of vascular stents seeded with different materials was tested. G/PLL- coated stents provided multiple advantages and bioactive benefits to the mesenchymal stem cells. On the other hand, SF/SDF-1α also promoted similar benefits but provoked multiple unwanted inflammatory responses. G/PLL and SF/SDF-1α coated stents were able to provide satisfactory results but still require more extensive research to thoroughly understand their efficacies and safety. Future directions may include researching and discovering a wider array of biocompatible materials to seed the stents.