rna-seq-reveals-th17-cell-differentiation-pathway-as-mechanism

RNA-Seq Reveals Th17 Cell Differentiation Pathway as a Mechanism of Radiation-Induced Brain Injury

Radiotherapy is a prevalent therapeutic modality for head and neck malignancies; however, it invariably results in radiation-induced damage to normal ...

Beijing Institute of Radiation Medicine

Mesenchymal stem cells (MSCs) are heterogeneous populations with broad application prospects in cell therapy, and using specific subpopulations of MSCs can enhance their particular capability under certain conditions and achieve better therapeutic effects. However, no studies have reported how to obtain high-quality specific MSC subpopulations in vitro culture. Here, for the first time, we established a general operation process for obtaining high-quality clinical-grade cell subpopulations from human umbilical cord MSCs (hUC-MSCs) based on particular markers. We used the MSC-CD106 subpopulations, whose biological function has been well documented, as an example to explore and optimize the crucial links of primary preparation, pre-treatment, antibody incubation, flow sorting, quality and function test. After comprehensively evaluating the quality and function of the acquired MSC-CD106 subpopulations, including in vitro cell viability, apoptosis, proliferation, marker stability, adhesion ability, migration ability, tubule formation ability, immunomodulatory function and in vivo wound healing ability and proangiogenic activity, we defined an important pre-treatment scheme which might effectively improve the therapeutic efficiency of MSC-CD106 subpopulations in two critical clinical application scenarios-direct injection after cell sorting and post-culture injection into bodies. Based on the above, we tried to establish a general five-step operation procedure for acquiring high-quality clinical-grade MSC subpopulations based on specific markers, which cannot only improve their enrichment efficiency and the reliability of preclinical studies, but also provide valuable methodological guidance for the rapid clinical transformation of specific MSC subpopulations.

An optimized method for obtaining clinical-grade specific cell subpopulations from human umbilical cord-derived mesenchymal stem cells.

With the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases. This study comprehensively evaluates the preclinical efficacy of clinical-grade hUC-MSCs in treating age-associated sarcopenia (AAS), and demonstrates that hUC-MSCs restore skeletal muscle strength and performance in two AAS mouse models via raising the expression of extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging, which highlights a promising strategy for AAS and other age-associated muscle diseases.

Clinical-grade human umbilical cord-derived mesenchymal stem cells improved skeletal muscle dysfunction in age-associated sarcopenia mice.

Dental trauma is highly prevalent in children and adolescents, alongside tooth decay. This condition mainly induces pulp contamination, pulp necrosis, and tooth avulsion in the clinical context. The disturbance to root growth is prone to occur in immature permanent teeth. However, conventional endodontic treatment may not achieve favorable outcomes in these cases, necessitating conducting relevant exploration. Therefore, this study was performed to examine the impact of Annexin A1 (ANXA1) on the vascular repair of dental pulp using human dental pulp stem cells (DPSCs). Specifically, RNA sequencing (RNA-Seq) and functional clustering analyses were employed to identify key genes involved in pulp regeneration. ANXA1 was detected in DPSCs and may correlate with pulp restoration. However, it remains undefined about the potential of ANXA1 to promote the angiogenetic differentiation of DPSCs. The results of this study revealed that the addition of ANXA1 significantly enhanced the secretion of vascular endothelial growth factor-A (VEGF-A) in DPSCs. Moreover, the incubation of DPSCs with ANXA1 resulted in a higher expression level of endothelial markers and promoted vessel formation through the upregulation of the phosphorylated p38 (p-p38) pathway. The in vivo results corroborated that the ANXA1 group exhibited more blood vessels and an increased ratio of positive staining for CD31. In conclusion, these findings indicate that ANXA1 enhances the in vivo and in vitro vascularization of DPSCs, and the activation of p-p38 may play a pivotal role in mediating the differentiation process.

ANXA1 Enhances the Proangiogenic Potential of Human Dental Pulp Stem Cells.

Bacterial traceability refers to the use of a range of techniques to trace the origins and transmission pathways of bacteria. It is crucial in controlling the spread of diseases, analyzing bioterrorism incidents, and advancing microbial forensics. In recent years, the frequency and scope of bacterial outbreaks have continued to escalate, exerting significant impacts on global biosecurity, public health, and other areas. Consequently, it is required to process traceability of bacteria timely and accurately around the globe. The rapid development of biological and physicochemical traceability techniques provides convenience for tracing bacteria. These techniques not only surpass traditional methods in terms of sensitivity, traceability and throughput, but also find more extensive applications in elucidating bacterial growth mechanisms, transmission routes, and geographical origins. This paper systematically reviews the latest research progress and applications of technologies of bacterial traceability, highlighting key advancements and projecting future trends, with the intent of providing a valuable reference for researchers, facilitating further studies and innovations in this field.

Research progress and application of bacterial traceability technology.

Neuroinflammation triggered by activated microglia leads to neuronal damage and, to a certain extent, neurodegeneration. Human umbilical cord mesenchymal stem cells (UC-MSCs) have good immunomodulatory and neuroprotective effects as well as therapeutic potential for neuroinflammation-related diseases. However, the complex microenvironment created by neuroinflammation poses a challenge to transplanted UC-MSCs. The emerging biomimetic microniche (BN)-based culture technology provides new opportunities to optimize the preparation of UC-MSCs; but the fundamental changes in the characteristics of UC-MSCs based on BN remain unclear, and more reliable preclinical data are needed to support their ability to regulate inflammation. Here, we systematically studied the cellular properties and inflammation regulatory capacity of UC-MSCs in conventional static planar culture (SP-UCMSCs) and suspension culture based on BN (BN-UCMSCs). In vitro, compared with SP-UCMSCs, BN-UCMSCs not only maintained the fundamental characteristics of MSCs, but also significantly enhanced cell proliferation, adhesion, and migration capabilities, etc; notably, the paracrine function and anti-inflammatory capacity of BN-UCMSCs were also enhanced. We further established a murine model of acute brain inflammation and demonstrated that the expression level of pro-inflammatory cytokines in hippocampal and cortical tissues of the BN-UCMSCs group was significantly decreased compared with that in the SP-UCMSCs group. Subsequent transcriptomic analysis of hippocampal and cortical tissues revealed that BN-UCMSCs had the advantage of significantly reducing the expression of pro-inflammatory cytokines through the TLR4-Myd88-NF-κB axis, which was further validated at the gene and protein levels. Taken together, these data strongly indicated that BN-UCMSCs exerts excellent regulatory effects on acute brain inflammation through advantageous properties.

Article	Year
An optimized method for obtaining clinical-grade specific cell subpopulations from human umbilical cord-derived mesenchymal stem cells. Cell proliferation\| PubMed ID: 35768999	2022
Clinical-grade human umbilical cord-derived mesenchymal stem cells improved skeletal muscle dysfunction in age-associated sarcopenia mice. Cell death & disease\| PubMed ID: 37173309	2023
ANXA1 Enhances the Proangiogenic Potential of Human Dental Pulp Stem Cells. Stem cells international\| PubMed ID: 39478978	2024
Research progress and application of bacterial traceability technology. Forensic science international\| PubMed ID: 39489139	2024
UC-MSCs based on biomimetic microniche exert excellent regulatory effects on acute brain inflammation through advantageous properties. Biomaterials\| PubMed ID: 39522143	2025

Bichun Zhao

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