Current stem cell research & therapy最新文献

Alzheimer's disease (AD), an inexorable neurodegenerative ailment marked by cognitive impairment and neuropsychiatric manifestations, stands as the foremost prevailing form of dementia in the geriatric population. Its pathological signs include the aggregation of amyloid proteins, hyperphosphorylation of tau proteins, and the consequential loss of neural cells. The etiology of AD has prompted the formulation of numerous conjectures, each endeavoring to elucidate its pathogenesis. While a subset of therapeutic agents has displayed clinical efficacy in AD patients, a significant proportion has encountered disappointment. Notably, the extent of neural cell depletion bears a direct correlation with the disease's progressive severity. However, the absence of efficacious therapeutic remedies for neurodegenerative afflictions engenders a substantial societal burden and exerts a notable economic toll. In the past two decades, the realm of regenerative cell therapy, referred to as stem cell therapy, has unfolded as an avenue for the exploration of profoundly innovative approaches to treat neurodegenerative conditions. This promise is underpinned by the remarkable capacity of stem cells to remediate compromised neural tissue by means of cell replacement, to cultivate an environment conducive to regeneration, and to shield extant healthy neuronal and glial components from further degradation. Thus, this review aims to delve into the current knowledge of stem cell-based therapies and future possibilities in this domain.

Background: Aging is a phenomenon which occurs over time and leads to the decay of living organisms. During the progression of aging, some age-associated diseases including cardiovascular disease, cancers, and neurological, mental, and physical disorders could develop. Genetic and epigenetic factors like microRNAs, as one of the post-transcriptional regulators of genes, play important roles in senescence. The self-renewal and differentiation capacity of mesenchymal stem cells makes them good candidates for regenerative medicine.

Objective: The objective of this study is to evaluate senescence-related miRNAs in human MSCs using bioinformatics analysis.

Methods: In this study, the Gene Expression Omnibus (GEO) database was used to investigate the senescence-related genome profile. Then, down-regulated genes were selected for further bioinformatics analysis with the assumption that their decreased expression is associated with an increased aging process. Considering that miRNAs can interfere in gene expression, miRNAs complementary to these genes were identified using bioinformatics software.

Results: Through bioinformatics analysis, we predicted hsa-miR-590-3p, hsa-miR-10b-3p, hsamiR- 548 family, hsa-miR-144-3p, and hsa-miR-30b-5p which involve in cellular senescence and the aging of human MSCs.

Conclusion: miRNA mimics or anti-miRNA agents have the potential to be used as anti-aging tools for MSCs.

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: Complications arising from diabetes can result in stem cell dysfunction, impairing their ability to undergo differentiation into various cellular lineages. The present study evaluated the effect of histone deacetylase inhibitors, Valproic acid and Trichostatin A, on the odontogenic differentiation potential of dental pulp stem cells under hyperglycemic conditions.

Methods: Streptozotocin (STZ) induced diabetes mellitus in 12 male Wistar rats. Dental parameters were examined using micro-computed tomography. The odontogenic potential of human pulp stem cells exposed to 30 mM glucose was assessed through alkaline phosphatase assays, examination of gene expression for dentin matrix protein 1 and dentin sialoprotein using real-time PCR, and alizarin red staining for calcium deposition.

Results: Along with reduced dentin thickness and root length in diabetic rats, the results revealed a significant increase in histone deacetylase 3 and 2 gene expressions in isolated diabetic pulp tissues compared to the control groups. The gene expression of odontogenic-related markers and alkaline phosphatase activity in human cultured pulp stem cells under hyperglycemic conditions significantly decreased. Adding Valproic acid and Trichostatin A restored the odontogenic differentiation markers, including calcium deposition, gene expression of dentin sialophosphoprotein, dentin matrix protein 1, and alkaline phosphatase activity.

Conclusion: The data suggests that hyperglycemic conditions negatively impact the odontogenic potential of pulp mesenchymal stem cells. However, histone deacetylase inhibitors improve the impaired odontogenic differentiation capacity. This study implies that histone deacetylases may represent a potential therapeutic target for enhancing the regenerative mineralization of pulp cells in diabetic patients.

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: To determine the effectiveness of bone marrow-derived mesenchymal stem cell therapy on visual acuity and visual field in patients with retinitis pigmentosa.

Objective: Stem cell treatment in retinitis pigmentosa provides improvement in visual acuity and visual field.

Method: Forty-seven eyes of 27 patients diagnosed with retinitis pigmentosa were included in our study. Allogeneic bone marrow-derived mesenchymal stem cells were administered by deep subtenon injection. Complete routine ophthalmological examinations, optical coherence tomography (Zeiss, Cirrus HD-OCT) measurements, and visual field (Humphrey perimetry, 30-2) tests were performed on all patients before the treatment and on the 1st, 3rd, and 6th month after treatment. The best corrected visual acuities of the patients were determined by the Snellen chart and converted to logMAR. Visual evoked potential (VEP) and electroretinogram (ERG) examinations of the patients before the treatment and on the 6th month after the treatment were performed (Metrovision) data were compared.

Results: Visual acuities were 0.74 ± 0.49 logMAR before treatment and 0.61 ± 0.46 logMAR after treatment. Visual acuity had a statistically significant increase (p < 0.001). The visual field deviation was found to be -27.16 ± 5.77 dB before treatment and -26.59 ± 5.96 dB after treatment (p = 0.005). The ganglion cell layer was 46.26 ± 12.87 μm before treatment and 52.47 ± 12.26 μm after treatment (p = 0.003). There was a significant improvement in Pattern VEP 120º P100 amplitude compared to that before the treatment (4.43 ± 2.42 μV) and that after the treatment (5.09 ± 2.86 μV) (p = 0.013). ERG latency measurements were 18.33 ± 15.39 μV before treatment and 20.87 ± 18.64 μV after treatment for scotopic 0.01 (p = 0.02). ERG latency measurements for scotopic 3.0 were 20.75 ± 26.31 μV before treatment and 23.10 ± 28.60 μV after treatment (p = 0.014).

Conclusion: Retinitis pigmentosa is a progressive, inherited disease that can result in severe vision loss. In retinitis pigmentosa, the application of bone marrow-derived mesenchymal stem cells by deep subtenon injection has positive effects on visual function. No systemic or ophthalmic side effects were detected in the patients during the 6-month follow-up period.

Background: While there is no certain treatment for spinal cord injury (SCI), stem cellbased therapy may be an attractive alternative, but the survival and differentiation of cells in the host tissue are poor. Conditioned medium (CM) has several beneficial effects on cells.

Objective: In this meta-analysis study, we examined the effect of CM on SCI treatment.

Methods: After searching on MEDLINE, SCOPUS, EMBASE, and Web of Science, first and secondary screening were performed based on title, abstract, and full text. The data were extracted from the included studies, and meta-analysis was performed using STATA.14 software. A standardized mean difference (SMD) with a 95% confidence interval was used to report findings. Quality control and subgroup analysis were also performed.

Results: The results from 52 articles and 61 separate experiments showed that CM had a significantly strong effect on improving motor function after SCI (SMD = 2.58; 95% CI: 2.17 to 2.98; p < 0.001) and also analysis of data from 12 articles demonstrated that CM reduced the expression of GFAP marker (SMD = -4.16; p < 0.0001) compared to SCI group without any treatment. Subgroup analysis showed that treatment with CM of neural stem cells was better than CM of mesenchymal stem cells. It was more effective after a mild lesion than a moderate or severe one. The improvement was more pronounced with <4 weeks than >4 weeks follow-up.

Conclusion: CM had a significant effect in improving motor function after SCI, especially in cases of mild lesions. It has been observed that if CM originates from the neural stem cells, it has a more significant effect than mesenchymal cells.

Background: Osteoporosis increases bone brittleness and the risk of fracture. Umbilical cord mesenchymal stem cell (UCMSC) treatment is effective, but how to improve the biological activity and clinical efficacy of UCMSCs has not been determined.

Methods: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 106 cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κβ ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, β-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting.

Results: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, β-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment.

Conclusion: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/β-catenin

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," "Cochrane Library," "Web of Science," "Embase," "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.