Potential Of Stem Cells Research Articles

Mapping chromatin remodelling in glioblastoma identifies epigenetic regulation of key molecular pathways and novel druggable targets

BackgroundGlioblastoma is the most common and aggressive malignant brain tumour in the adult population and its prognosis is dismal. The heterogeneous nature of the tumour, to which epigenetic dysregulation significantly contributes, is among the main therapeutic challenges of the disease.ResultsWe have leveraged SYNGN, an experimental pipeline enabling the syngeneic comparison of glioblastoma stem cells and expanded potential stem cell (EPSC)-derived neural stem cells to identify regulatory features driven by chromatin remodelling specifically in glioblastoma stem cells.ConclusionsWe show epigenetic regulation of the expression of genes and related signalling pathways contributing to glioblastoma development. We also identify novel epigenetically regulated druggable target genes on a patient-specific level, including SMOX and GABBR2.

Enucleated bone marrow-derived mesenchymal stromal cells regulate immune microenvironment and promote testosterone production through efferocytosis

BackgroundTestosterone deficiency (TD) occurs most frequently in older men and can cause many health problems. Testosterone replacement therapy (TRT) is widely used to treat TD, but this regimen can lead to a series of side effects. Stem cell therapy has been wildly studied in vitro. However, due to the multidirectional differentiation potential and heterogeneity of stem cells, it is difficult to achieve the good efficiency and reproducibility in basic research and clinical applications. This study aims to identify a new strategy for the treatment of TD.MethodsBone marrow-derived mesenchymal stromal cells (BMSCs) were enucleated by Ficoll density gradient centrifugation. The organelles and cellular functions of enucleated BMSCs were analyzed by immunofluorescence staining and flow cytometry. Extracellular vesicles (EVs) were isolated by ultracentrifugation and characterized. For the animal studies, enucleated BMSCs were labelled with Mitotracker and injected into ethane dimethanesulfone (EDS)-treated rats. Testosterone production and spermatogenesis were detected at different time points through various tests. To determine the mechanism of efferocytosis, we analysed the number of macrophages by immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe injection of enucleated BMSCs (Cargocytes) into the testes of EDS-treated rats restored the levels of serum testosterone, increased the number of Leydig cells (LCs), and improved spermatogenesis. We found that enucleated BMSCs underwent apoptosis earlier than BMSCs did. Subsequently, testicular interstitial macrophages phagocytosed apoptotic enucleated BMSCs through efferocytosis. Efferocytosis promoted macrophage polarization from the M1 to the M2 phenotype, reduced the expression of proinflammatory cytokines, and decreased the levels of inflammation and oxidative stress.ConclusionsIn summary, this study pioneered the application of stromal cell enucleation technology to repair tissue damage in the reproductive system, explored the potential of cell burial in the treatment of reproductive system diseases and provided a new approach for the clinical treatment of male infertility.

Testosterone in long-term sedentary aging males: Effect of antiaging strategies.

Physical activity can provide health benefits if done regularly and of sufficient duration and intensity. TheWorld Health Organization recommends adults do 150-300 min of moderate-intensity activity per week, 75-150 min of vigorous-intensity activity, or an equivalent combination.Physical inactivity is the fourth leading cause of early death globally, with 31% of the world's population not getting enough physical activity. Aging is defined by rapid decline in physical activity, loss of mobility, and premature morbidity.Low testosterone levels in men decline from 30 to 40 years of age, and this continues until death. Antiaging strategies, such as caloric restriction, balanced diet, regular exercise, weight management, diabetes control, and smoking cessation can prevent and treat aging-related diseases. Exercise significantly boosts testosterone production, with levels varying based on type, frequency, volume, intensity, and duration. It increases muscle steroidogenesis, total testosterone, and free testosterone in the elderly. Testosterone replacement therapy in elderly men improves physical function, strength, protein synthesis, cholesterol, bone density, sexual desire, erectile function, and overall cognition. However, some studies suggest dehydroepiandrosterone supplementation may provide health improvements without negative effects, potentially reversing arterial aging and reducing the risk of cardiovascular diseases. Senolytic therapeutics focus on cellular senescence, and stem cell transplantation investigates the therapeutic potential of older stem cells.

Expansion of induced pluripotent stem cells under consideration of bioengineering aspects: part 1

To fully utilize the potential of human induced pluripotent stem cells (hiPSCs) for allogeneic stem cell–based therapies, efficient and scalable expansion procedures must be developed. For other adherent human cell types, the combination of microcarriers (MCs) and stirred tank bioreactors has been shown to meet these demands. In this study, a hiPSC quasi-perfusion expansion procedure based on MCs was developed at 100-mL scale in spinner flasks. Process development began by assessing various medium exchange strategies and MC coatings, indicating that the hiPSCs tolerated the gradual exchange of medium well when cultivated on Synthemax II–coated MCs. This procedure was therefore scaled-up to the 1.3-L Eppendorf BioBLU 1c stirred tank bioreactor by applying the lower limit of Zwietering’s suspension criterion (Ns1u), thereby demonstrating proof-of-concept when used in combination with hiPSCs for the first time. To better understand the bioreactor and its bioengineering characteristics, computational fluid dynamics and bioengineering investigations were performed prior to hiPSC cultivation. In this manner, improved process understanding allowed an expansion factor of ≈ 26 to be achieved, yielding more than 3 × 109 cells within 5 days. Further quality analyses confirmed that the hiPSCs maintained their viability, identity, and differentiation potential throughout cultivation.Key points• Ns1u can be used as a scale-up criterion for hiPSC cultivations in MC-operated stirred bioreactors• Uniform distribution and attachment of cells to the MCs are crucial for efficient expansion• Perfusion is advantageous and supports the cultivation of hiPSCs

Toward Machine Learning Electrospray Ionization Sensitivity Prediction for Semiquantitative Lipidomics in Stem Cells.

Specificity, sensitivity, and high metabolite coverage make mass spectrometry (MS) one of the most valuable tools in metabolomics and lipidomics. However, translation of metabolomics MS methods to multiyear studies conducted across multiple batches is limited by variability in electrospray ionization response, making batch-to-batch comparisons challenging. This limitation creates an artificial divide between nontargeted discovery work that is broad in scope but limited in terms of absolute quantitation ability and targeted work that is highly accurate but limited in scope due to the need for matched isotopically labeled standards. These issues are often observed in stem cell studies using metabolomic and lipidomic MS approaches, where patient recruitment can be a years-long process and samples become available in discrete batches every few months. To bridge this gap, we developed a machine learning model that predicts electrospray ionization sensitivity for lipid classes that have shown correlation with stem cell potency. Molecular descriptors derived from these lipids' chemical structures are used as model input to predict electrospray response, enabling quantitation by MS with moderate accuracy (semiquantitation). Model performance was evaluated via internal and external validation using cultured cells from various stem cell donors, achieving global percent errors of 40% and 20% for positive and negative electrospray ion modes, respectively. Although this accuracy is typically insufficient for traditional targeted lipidomics experiments, it is sufficient for semiquantitative estimation of lipid marker concentrations across batches without the need for specific chemical standards that many times are unavailable. Furthermore, the precision for model-predicted concentrations was 16.9% for the positive mode and 7.5% for the negative mode, indicating promise for data harmonization across batches. The set of molecular descriptors used by the models described here was able to yield higher accuracy than those previously published in the literature, showing high promise toward semiquantitative lipidomics.

Loss of 18q Alters TGFβ Signalling Affecting Anteroposterior Neuroectodermal Fate in Human Embryonic Stem Cells.

Chromosomal abnormalities acquired during cell culture can compromise the differentiation potential of human pluripotent stem cells (hPSCs). In this work, we identified a diminished differentiation capacity to retinal progenitor cells in human embryonic stem cells (hESCs) with complex karyotypes that had in common the loss of part of chromosome 18q. Time-course gene-expression analysis during spontaneous differentiation and single-cell RNA sequencing found that these variant cell lines poorly specified into anterior neuroectoderm, and, when progressing through differentiation, they yielded poorly pigmented cells, with proliferating and pluripotent cell populations. The variant cell lines showed dysregulation of TGFβ signalling during differentiation, and chemical modulation of the TGFβ pathways showed that the basis of the improper specification was due to imbalances in the anteroposterior neuroectodermal fate commitment.

Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank

BackgroundInduced pluripotent stem cells (iPSCs) can differentiate into any type of cell and have potential uses in regenerative medicine for the treatment of many diseases. However, reducing immune rejection is a key problem in the application of iPSCs that can be solved by the development of haplobanks containing specially selected iPSC lines.MethodsTo study the feasibility of constructing an HLA (human leukocyte antigen)-matched induced pluripotent stem cell haplobank in China, 5421 umbilical cord blood samples were randomly collected from the Umbilical Cord Blood Bank of Zhejiang Province, China. The HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci were genotyped using next-generation sequencing. Using HLA genotype data at the high-resolution level, the number of HLA homozygous donors needed to cover a certain percentage of the Chinese population and the feasibility of constructing a high-matching iPSC haplobank were estimated.ResultsThirteen HLA-A, -B, and -DRB1 and 11 HLA-A, -B, -C, -DRB1, and -DQB1 haplotype homozygotes were observed among the stored umbilical CB units which were as HLA zero-mismatched iPSC donors cumulatively matched 37.01% and 32.99% of 5421 potential patients respectively. The analysis showed that 100 distinct HLA-A, -B, and -DRB1 and HLA-A, -B, -C, -DRB1, and -DQB1 homozygous haplotypes would cover 72.74% and 67.87% of Chinese populations, respectively, and 600 HLA-A, -B, -C, -DRB1, and -DQB1 homozygous haplotypes would cover more than 90% of Chinese populations. PCA (principal component analysis) of published HLA data from different populations revealed that the frequency of these haplotypes in Asian populations is different from those in European populations.ConclusionThe results suggested that at least some HLA-homozygous iPSC lines developed from Chinese individuals will not only be useful for covering the Chinese population but will also cover other Asian populations. A high-matching iPSC haplobank generated from umbilical CB units may be an economical and effective option in an allogeneic model of iPSC therapy.

ERK phosphorylates ESRRB to regulate the self-renewal and differentiation of mouse embryonic stem cells.

MEK (mitogen-activated protein kinase) inhibitor is widely used for culturing pluripotent stem cells, while prolonged MEK inhibition compromises the developmental potential of mouse embryonic stem cells (ESCs), implying a dual role of MEK/ERK (extracellular signal-regulated kinase) signaling in pluripotency maintenance. To better understand the mechanism of MEK/ERK in pluripotency maintenance, we performed quantitative phosphoproteomic analysis and identified 169 ERK substrates, which are enriched for proteins involved in stem cell population maintenance, embryonic development, and mitotic cell cycle. Next, we demonstrated that ERK phosphorylates a well-known pluripotency factor ESRRB on Serine 42 and 43. Dephosphorylation of ESRRB facilitates its binding to pluripotency genes, thus enhancing its activity to maintain pluripotency. In contrast, phosphorylation of ESRRB increases its binding to extraembryonic endoderm (XEN) genes, consequently promoting XEN differentiation of ESCs. Altogether, our study reveals that ERK may regulate ESC self-renewal and differentiation by phosphorylating multiple substrates, including ESRRB, which affects both ESC self-renewal and XEN differentiation.

Anti-Inflammatory Resveratrol Protects Mice From Early Mortality After Haematopoietic Stem Cell Transplantation.

The occurrence of inflammation subsequent to haematopoietic stem cell transplantation is associated with an elevated risk of transplant-related mortality (TRM). However, the duration of inflammation and the potential efficacy of anti-inflammatory agents in reducing TRM remain uncertain. We performed a comprehensive investigation to examine the post-transplantation alterations of inflammatory mediators and to ascertain the correlation between inflammation level and TRM through the neutrophil-lymphocyte ratio, ELISAs and cytometric bead array. The findings revealed that the 30-day interval following transplantation is characterised by the most pronounced inflammatory response in both human and murine subjects, thereby elevating the risk of TRM. The inflammation is primarily caused by myeloid bias during haematopoietic reconstitution, which is a commonly overlooked aspect in clinical transplantation, additionally, a lesser extent of irradiation-induced injury. The administration of the anti-inflammatory agent resveratrol has the potential to reduce systemic inflammation and TRM by suppressing the NOD-like receptor signalling pathway and slowing down granulocyte implantation in HSCT mice. This approach did not impair the differentiation potential of haematopoietic stem cells. These findings demonstrate that the 30-day post-transplant period represents an opportunity to facilitate HSCT colonisation, mitigate transplant-related adverse effects, and potentially reap the benefits of anti-inflammatory treatments.

Novel Combination of Traditional Ayurvedic Herb Piper longum L. and Modern Stem Cell Therapy for the Reversal of Glucocorticoid-Induced Osteoporosis.

Glucocorticoids induced osteoporosis (GIOP) is a global concern without effective therapies. The present study investigated the potential of the umbilical cord-derived mesenchymal stem cells (UCMSCs) and traditional medicine Piper longum L. in the reversal of GIOP. Twelve-week-old female Swiss Albino mice were subjected to the dexamethasone treatment for 4 weeks to induce GIOP. Further, the mice were randomized into four different groups for treatment, viz., phosphate buffered saline (PBS), UCMSCs, P. longum L. aqueous extract through feed, and a combination of UCMSCs and P. longum L. extract. Post therapy, GIOP mice regained the weight and hair loss in the UCMSCs and P. longum L. extract group. ALP activity and mRNA expression of RunX2, ALP, and OPN were significantly increased. Micro-CT analysis revealed remarkable improvement in key parameters such as bone volume, bone surface density, tissue surface, trabecular thickness, and number. Our results unequivocally demonstrate that a combination of the UCMSCs and P. longum L. is highly effective in the reversal of GIOP as compared to P. longum L. or UCMSCs alone. The therapeutic effect can be attributed to the osteogenic and paracrine potential of UCMSCs and the anti-inflammatory effect of P. longum L.

Therapeutic potential of mesenchymal stem cells for fungal infections: mechanisms, applications, and challenges

Therapeutic potential of mesenchymal stem cells for fungal infections: mechanisms, applications, and challenges

SIRT5 -mediated desuccinylation of UQCRC2 attenuates osteogenic differentiation of aged BM-MSCs through impairing mitochondrial homeostasis.

The osteogenic differentiation potential of bone marrow mesenchymal stem cells (BM-MSCs) is critical for bone regeneration and repair. In recent years, the role of protein succinylation modification in regulating cellular metabolism has garnered increasing attention. However, its mechanism in osteogenic differentiation remains unclear. Oxygen consumption rate (OCR) and mitochondrial ROS (mtROS) were detected to assess mitochondrial function in BM-MSCs with successive passages. Alizarin red staining and western blot experiments were used to evaluate osteogenic differentiation capacity. .Succinylation modification omics and Co-IP detection were conducted to determine SIRT5-mediated desuccinylation of UQCRC2 . Bioinformatics analysis revealed that sirtuin 5 (SIRT5) expression is upregulated with multiple rounds of BM-MSCs' passages, and is associated with biological pathways such as oxidative phosphorylation (OXPHOS), cellular senescence, and inhibition of osteogenic differentiation. Experiments in vitro confirmed the up-regulation of SIRT5 and the suppression of osteogenic differentiation with the increased times of BM-MSCs' passages. Overexpression of SIRT5 enhanced OXPHOS and elevated mtROS levels, but reduced the expression of Runx2 and osteocalcin, and decreased calcified nodules, thereby inhibiting the osteogenic differentiation of BM-MSCs. SIRT5-mediated desuccinylation of ubiquinol-cytochrome C reductase core protein 2 (UQCRC2) at the site of K250 promoted UQCRC2 translocation from cytoplasm to mitochondria, which enhanced the activity of mitochondrial respiratory complex III. It further increased mtROS, accelerated cellular senescence and inhibited the osteogenic differentiation of BM-MSCs. SIRT5 reduces succinylation modification of UQCRC2, promotes mitochondrial respiration and mtROS, and thus reduces the osteogenic differentiation ability of BM-MSCs cells. SIRT5 might be a potential target to prevent the suppression of osteogenic differentiation of of BM-MSCs after multiple rounds passages.

Age-Associated Activation of the cGAS-STING Pathway and Impairment of DNA Damage Repair in Human Primary Alveolar Type II Cells.

Homeostatic imbalance and lung function decline are central physiological characteristics of aging and susceptibility to respiratory diseases. Senescence contributes to tissue damage and alveolar epithelial cell injury and decreases reparative capacity. Alveolar type II (ATII) cells have stem cell potential and self-renew to regenerate the alveoli after damage. They were isolated from younger and older non-smoker and smoker organ donors to define their function in the lung. Smoking and older age increased ATII cell senescence as detected by high β-galactosidase activity and P21 levels by Western blotting and RT-PCR. Also, the number of ATII cells was the lowest in lung tissue in older smokers. This was associated with increased stress signaling, as shown by elevated 4-HNE and G3BP1 expression in ATII cells, and inflammation indicated by high IL-8 levels in BAL fluid. In addition, DNA damage and decreased repair were observed using the comet assay, especially in ATII cells isolated from older smokers. This was accompanied by the highest levels of cytosolic double-strand DNA in this group and correlated with the activated cGAS-STING pathway and increased IRF3 expression. Moreover, telomere shortening, accumulation of TERRA molecules, and increased ZBP1 protein expression in ATII cells were associated with smoking and older age. Reduced NRF2 and DJ-1 expression in ATII cells was detected by Western blotting, especially in older smokers, which suggests an antioxidant defense system dysfunction. Our study provides insights into the impaired interconnected signaling network, which can contribute to ATII cell senescence.

Immunopathological characteristics and therapeutic effects of UC-MSCs in a pigeon breeder's lung mouse model.

Hypersensitivity pneumonitis (HP), including pigeon breeder's lung (PBL), often progresses from acute inflammation to fibrosis, impairing lung function and limiting targeted therapeutic strategies. Mechanistic studies on PBL progression are limited by the lack of preclinical animal models and a predominant focus on patient data. This study explores the immunopathological characteristics of all stages of PBL in mice and evaluates the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) during the non-fibrotic stage. PBL models are created in A/J mice through tracheal instillation of pigeon dropping extract (PDE) protein powder. Different doses (0.4 × 10 6, 0.8 × 10 6, and 1.6 × 10 6 cells per animal) and frequencies (1-2 times) are administered to the model. The immunopathological characteristics of PBL and the therapeutic effects of UC-MSCs are assessed using micro-CT, pulmonary function, histopathology, cell counts in BALF, HYP levels, inflammatory factor levels, immunohistochemistry, and fibrosis marker expression in lung tissues. The results show that PDE exposure consistently impairs pulmonary function and increases the levels of inflammation and fibrosis markers as the disease progresses. Model mice experience non-fibrotic stages (acute inflammation) from days 0-36, mild fibrosis from days 37-77, and severe fibrosis from day 78 onwards. UC-MSCs, particularly at the highest dose (1.6 × 10 6 cells), effectively treat non-fibrotic PBL by improving pulmonary function (lung ventilation area recovers) and reducing inflammation and fibrosis. This study successfully establishes PBL mouse models reflecting both the acute (inflammatory) and chronic (fibrotic) stages, and UC-MSCs have the potential to delay fibrosis, providing new therapeutic options for PBL and other inflammation-induced lung fibrotic diseases.

Promoting epithelial regeneration in chemically induced acute lung injury through Sox9-positive alveolar type 2 epithelial cells

BackgroundChemical-induced acute lung injury is characterized by impaired epithelial regenerative capacity, leading to acute pulmonary edema. Numerous studies have investigated the therapeutic potential of endogenous stem cells with particular emphasis on alveolar type 2 epithelial (AEC2) cells owing to their involvement in lung cell renewal. Sox9, a transcription factor known for its role in maintaining stem cell properties and guiding cell differentiation, marks a subset of AEC2 cells believed to contribute to epithelial repair. However, the role of Sox9+AEC2 cells in the distal lung alveolar cells and the potential roles in chemically induced acute lung injury have never been explored.MethodsIn this study, we generated Sox9flox/flox;SftpcCre−ERT2 mice and examined the effects of Sox9+AEC2 cells on the pathophysiology of epithelial damage during chemical-induced acute lung injury. Subsequently, Sox9-CreERT2 Ai9 mice were used for lineage tracing to elucidate the repair mechanisms.ResultsOur findings revealed that Sox9+AEC2 cells endowed with stem cell properties induced cell proliferation during lung injury, predominantly in the damaged alveolar region. This process is accompanied by the regulation of inflammatory responses and orderly differentiation, thereby promoting epithelial regeneration.ConclusionThese results provide compelling in vivo genetic evidence supporting the characterization of Sox9+AEC2 cells as bona fide lung epithelial stem cells, demonstrating their multipotency and self-renewal capabilities during lung repair and regeneration. The identification of Sox9+AEC2 cells as crucial contributors to the promotion of epithelial repair underscores their potential as therapeutic targets in chemical-induced acute lung injury.

PBCS-ConvNeXt: Convolutional Network-Based Automatic Diagnosis of Non-alcoholic Fatty Liver in Abdominal Ultrasound Images.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition characterized by excessive hepatic fat accumulation. Early diagnosis is crucial as NAFLD can progress to more severe conditions like steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma without timely intervention. While liver biopsy remains the gold standard for NAFLD assessment, abdominal ultrasound (US) imaging has emerged as a widelyadopted non-invasive modality due to convenience and low cost. However, the subjective interpretation of US images is challenging and unpredictable. This study proposes a deep learning-based computer-aided diagnosis (CAD) model, termed potent boosts channel-aware separable intent - ConvNeXt (PBCS-ConvNeXt), for automated NAFLD classification using B-mode US images. The model architecture comprises three key components: The potent stemcell, an advanced trainable preprocessing module for robust feature extraction; Enhanced ConvNeXt Blocks that amplify channel-wise features to refine processing; and the boosting block that integrates multi-stage features for effective information extraction from US data. Utilizing fatty liver gradings from attenuation imaging (ATI) as the ground truth, the PBCS-ConvNeXt model was evaluated using 5-fold cross-validation, achieving an accuracy of 82%, sensitivity of 81% and specificity of 83% for identifying fatty liver on abdominal US. The proposed CAD system demonstrates high diagnostic performance in NAFLD classification from US images, enabling early detection and informing timely clinical management to prevent disease progression.

Modulation of PRL-1 within placental MSCs instigates the transition between EMT and MET subsequent to hepatic fibrosis.

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease. Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver-1 (PRL-1) in promoting liver regeneration. We evaluated the efficacy of PD-MSCs overexpressing PRL-1 (PD-MSCsPRL-1) in a bile duct ligation (BDL)-induced rat injury model, focusing on their ability to regulate EMT. PD-MSCsPRL-1 significantly reduced mesenchymal markers by downregulating TGFB1/SMAD2, outperforming naïve PD-MSCs. The transplantation of PD-MSCsPRL-1 enhanced BMP7/SMAD1/5 expression, promoting epithelial marker expression and stimulating BMP7 within hepatocytes, modulating downstream SMAD signaling. Importantly, further validation confirmed that PRL-1 directly interacts with BMP7 in hepatocytes. PRL-1 expression in PD-MSCsPRL-1 restores TGFB1/BMP7 balance, promoting hepatic regeneration through mesenchymal-to-epithelial transition (MET). These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies.

Therapeutic Potential of Menstrual Blood-Derived Stem Cells in Attenuating Uterine Adhesion: Novel Strategies and Future Prospect.

Intrauterine Adhesions (IUAs) are characterized by endometrial damage due to endometritis or curettage. Currently, the gold standard for IUA treatment is hysteroscopy, which enables the dissolution of IUA through mechanical or electrosurgical energy. Common strategies to prevent recurrence include the insertion of a balloon catheter or IUD in the uterus. Although hysteroscopy and postoperative strategies improve the uterine cavity's morphology and menstrual flow in some patients, infertility and adhesion recurrence rates are among the problems that persist. Mesenchymal Stem Cells (MSCs) are ideal for tissue regeneration due to their self-renewal and immunomodulatory characteristics. MSCs also exert anti-fibrotic properties in IUA treatment. However, the clinical application of stem cells is limited due to safety concerns and cost. In this review, we have summarized the recent advances in the application of MSCs in IUA treatment.

Exploring the Potential of Stem Cells in Modulating Gut Microbiota and Managing Hypertension.

Hypertension, commonly known as high blood pressure, is a significant health issue that increases the risk of cardiovascular diseases, stroke, and renal failure. This condition broadly encompasses both primary and secondary forms. Despite extensive research, the underlying mechanisms of systemic arterial hypertension-particularly primary hypertension, which has no identifiable cause and is affected by genetic and lifestyle agents-remain complex and not fully understood. Recent studies indicate that an imbalance in gut microbiota, referred to as dysbiosis, may promote hypertension, affecting blood pressure regulation through metabolites such as short-chain fatty acids and trimethylamine N-oxide. Current antihypertensive medications face limitations, including resistance and adherence issues, highlighting the need for novel therapeutic approaches. Stem cell therapy, an emerging field in regenerative medicine, shows promise in addressing these challenges. Stem cells, with mesenchymal stem cells being a prime example, have regenerative, anti-inflammatory, and immunomodulatory properties. Emerging research indicates that stem cells can modulate gut microbiota, reduce inflammation, and improve vascular health, potentially aiding in blood pressure management. Research has shown the positive impact of stem cells on gut microbiota in various disorders, suggesting their potential therapeutic role in treating hypertension. This review synthesizes the recent studies on the complex interactions between gut microbiota, stem cells, and systemic arterial hypertension. By offering a thorough analysis of the current literature, it highlights key insights, uncovers critical gaps, and identifies emerging trends that will inform and guide future investigations in this rapidly advancing field.

Stem Cell Therapy for Diseases of Livestock Animals: An In-Depth Review.

Stem cells are unique, undifferentiated cells that have the ability to both replicate themselves and develop into specialized cell types. This dual capability makes them valuable in the development of regenerative medicine. Current development in stem cell research has widened their application in cell therapy, drug discovery, reproductive cloning in animals, and cell models for various diseases. Although there are substantial studies revealing the treatment of human degenerative diseases using stem cells, this is yet to be explored in livestock animals. Many diseases in livestock species such as mastitis, laminitis, neuromuscular disorders, autoimmune diseases, and some debilitating diseases are not covered completely by the existing drugs and treatment can be improved by using different types of stem cells like embryonic stem cells, adult stem cells, and induced pluripotent stem cells. This review mainly focuses on the use of stem cells for disease treatment in livestock animals. In addition to the diseases mentioned, the potential of stem cells can be helpful in wound healing, skin disease therapy, and treatment of some genetic disorders. This article explores the potential of stem cells from various sources in the therapy of livestock diseases and also their role in the conservation of endangered species as well as disease model preparation. Moreover, the future perspectives and challenges associated with the application of stem cells in livestock are discussed. Overall, the transformative impact of stem cell research on the livestock sector is comprehensively studied which will help researchers to design future research work on stem cells related to livestock diseases.