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Parkinson's disease (PD) is one of the fastest-growing neurodegenerative disorders worldwide. So far, PD treatments only offer little clinical relief and cannot reverse or stop the disease progression. Stem cell (SC) therapy is a rapidly evolving technology that holds significant promise for enhancing current therapeutic approaches. Adipose-derived mesenchymal SCs (AD-MSCs) have many features such as easy harvest with minimal invasive techniques, high plasticity, non-immunogenicity, and no ethical issues, which have made them suitable choices for clinical applications in regenerative research. AD-MSCs are ideal tools to treat PD, as they have the potential to differentiate into functional dopaminergic neurons, and also could produce and secrete useful paracrine factors and extracellular vesicles, such as cytokines and growth factors, and thus promote the repair and regeneration of damaged nerve tissue. Studies revealed that AD-MSCs induced angiogenesis, nerve regeneration, and memory and motor improvement in cellular and animal models of PD. Moreover, clinical studies demonstrated the safety of AD-MSC transplantation in PD patients. This review provides a comprehensive and current summary of the therapeutic potential of AD-MSC transplantation for the treatment of PD, by highlighting the ability of cells to differentiate into functional dopaminergic neurons. [ABSTRACT FROM AUTHOR]

Objective(s): Enhancement of proliferation, pluripotency, and self-renewal capacity as the unique features of MSCs can improve their therapeutic potential to regenerate tissues. In this context, crocin and curcumin, carotenoid compounds with outstanding medicinal properties, could be promising for cell protection and growth. This study aimed to evaluate the impact of nanocurcumin and crocin on BM-MSCs proliferation and pluripotency in vitro. Materials and Methods: BM-MSC were isolated from the iliac crest of SCI patients who were candidates for stem cell therapy. The effect of crocin and nanocurcumin on MSC proliferation was evaluated using MTT and PDT assay. The percentage of apoptotic MSCs was measured by flow cytometry. Furthermore, mRNA and protein expression of OCT4 and SOX2 as the proliferation and self-renewal related genes were quantified by real-time PCR and western blotting, respectively. Results: Our findings demonstrated that only low concentrations of nanocurcumin (0.3 and 0.7 µM) and crocin (2.5 5 µM) significantly affected MSCs proliferation and protected them from apoptosis. Also, crocin and nanocurcumin at low doses caused an elevation in the mRNA and protein expression levels of OCT4 and SOX2 genes. In contrast, high concentrations decreased the survival of MSCs and led to increased apoptosis compared with the untreated group. Conclusion: Our results suggest that using nanocurcumin and crocin separately in culturing MSCs can be considered proliferative agents to prepare the more advantageous tool for cell therapies. However, more in vitro and preclinical research is needed in this area. [ABSTRACT FROM AUTHOR]

Asthma is a widespread public health concern, with an increasing incidence. Despite the implementation of current treatment strategies, asthma control, particularly for severe cases, remains suboptimal. Recent research has revealed the encouraging prospects of extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) as a viable therapeutic option for alleviating asthma symptoms. Therefore, the present review aims to provide an overview of the current progress and the therapeutic mechanisms of using MSC-derived EVs (MSC-EVs) for asthma treatment. Additionally, different administration approaches for EVs and their impacts on biodistribution and the curative outcomes of EVs are summarized. Notably, the potential benefits of nebulized inhalation of MSC-EVs are addressed. Also, the possibilities and challenges of using MSC-EVs for asthma treatment in clinics are highlighted. Overall, this review is intended to give new insight into the utilization of MSC-EVs as a potential biological drug for asthma treatment. [ABSTRACT FROM AUTHOR]

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the “golden communicators” between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes. [ABSTRACT FROM AUTHOR]

Mesenchymal stem and stromal cells (MSCs) hold potential to treat a broad range of clinical indications, but clinical translation has been limited to date due in part to challenges with batch-to-batch reproducibility of potential critical quality attributes (pCQAs) that can predict potency/efficacy. Here, we designed and implemented a microcarrier-microbioreactor approach to cell therapy manufacturing, specific to anchorage-dependent cells such as MSCs. We sought to assess whether increased control of the biochemical and biophysical environment had the potential to create product with consistent presentation and elevated expression of pCQAs relative to established manufacturing approaches in tissue culture polystyrene (TCPS) flasks. First, we evaluated total cell yield harvested from dissolvable, gelatin microcarriers within a microbioreactor cassette (Mobius Breez) or a flask control with matched initial cell seeding density and culture duration. Next, we identified 24 genes implicated in a therapeutic role for a specific motivating indication, acute respiratory distress syndrome (ARDS); expression of these genes served as our pCQAs for initial in vitro evaluation of product potency. We evaluated mRNA expression for three distinct donors to assess inter-donor repeatability, as well as for one donor in three distinct batches to assess within-donor, inter-batch variability. Finally, we assessed gene expression at the protein level for a subset of the panel to confirm successful translation. Our results indicated that MSCs expanded with this microcarrier-microbioreactor approach exhibited reasonable donor-to-donor repeatability and reliable batch-to-batch reproducibility of pCQAs. Interestingly, the baseline conditions of this microcarrier-microbioreactor approach also significantly improved expression of several key pCQAs at the gene and protein expression levels and reduced total media consumption relative to TCPS culture. This proof-of-concept study illustrates key benefits of this approach to therapeutic cell process development for MSCs and other anchorage-dependent cells that are candidates for cell therapies. [ABSTRACT FROM AUTHOR]

With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like poor wound healing, aging, and pigmentation have an impact not only on appearance but also on patients with physical and psychological issues, and even impose a significant financial burden on families and society. However, due to the complexities of its occurrence, present treatment options cannot produce optimal outcomes, indicating a dire need for new and effective treatments. Mesenchymal stem cells (MSCs) and their secretomics treatment is a new regenerative medicine therapy that promotes and regulates endogenous stem cell populations and/or replenishes cell pools to achieve tissue homeostasis and regeneration. It has demonstrated remarkable advantages in several skin-related in vivo and in vitro investigations, aiding in the improvement of skin conditions and the promotion of skin aesthetics. As a result, this review gives a complete description of recent scientific breakthroughs in MSCs for skin aesthetics and the limitations of their clinical applications, aiming to provide new ideas for future research and clinical transformation. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to consolidate the currently available literature regarding the treatment of neurogenic bladder (NGB) with stem cells or neural progenitor cells (NPCs). Recent Findings: Several promising studies published in the past 5 years suggest therapeutic potential of stem cells in treating NGB. In vitro models of NGB have demonstrated the efficacy of stem cells from varying sources to induce nerve regeneration while simultaneously improving bladder function parameters. Additionally, mesenchymal stem cells (MSCs) were found to inhibit fibrosis through the TGF-β1 signaling pathway while their effects were potentiated by elevated levels of BDNF or SDF-1. Among induced pluripotent stem cells (iPSCs), it was noted that autophagy inducers improved regenerative effects. NPCs, in a recent clinical trial, also underscored the potential for translating stem cell therapies into practice. Summary: Stem cells offer a potentially revolutionary regenerative medicine strategy for treatment of NGB. Many in vivo trials are promising, but there is a distinct shortage of clinical trials attempting to translate this success into human subjects. In the future, research should be directed towards understanding the complex mechanisms of stem cell-based therapy while moving towards the clinical applications of the technology. [ABSTRACT FROM AUTHOR]

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Background: The characteristics and therapeutic potential of subtypes of bone marrow mesenchymal stem cells (BMSCs) are largely unknown. Also, the application of subpopulations of BMSCs in cartilage regeneration remains poorly characterized. The aim of this study was to explore the regenerative capacity of CD146-positive subpopulations of BMSCs for repairing cartilage defects. Methods: CD146-positive BMSCs (CD146 + BMSCs) were sorted by self-developed CD146-specific lipid magnetic spheres (CD146-LMS). Cell surface markers, viability, and proliferation were evaluated in vitro. CD146 + BMSCs were subjected to in vitro chondrogenic induction and evaluated for chondrogenic properties by detecting mRNA and protein expression. The role of the CD146 subpopulation of BMSCs in cartilage damage repair was assessed by injecting CD146 + BMSCs complexed with sodium alginate gel in the joints of a mouse cartilage defect model. Results: The prepared CD146-LMS had an average particle size of 193.7 ± 5.24 nm, an average potential of 41.9 ± 6.21 mv, and a saturation magnetization intensity of 27.2 Am2/kg, which showed good stability and low cytotoxicity. The sorted CD146 + BMSCs highly expressed stem cell and pericyte markers with good cellular activity and cellular value-added capacity. Cartilage markers Sox9, Collagen II, and Aggrecan were expressed at both protein and mRNA levels in CD146 + BMSCs cells after chondrogenic induction in vitro. In a mouse cartilage injury model, CD146 + BMSCs showed better function in promoting the repair of articular cartilage injury. Conclusion: The prepared CD146-LMS was able to sort out CD146 + BMSCs efficiently, and the sorted subpopulation of CD146 + BMSCs had good chondrogenic differentiation potential, which could efficiently promote the repair of articular cartilage injury, suggesting that the sorted CD146 + BMSCs subpopulation is a promising seed cell for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Although several transcriptome-wide association studies (TWASs) have been performed to identify genes associated with overall breast cancer (BC) risk, only a few TWAS have explored the differences in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer. Additionally, these studies were based on gene expression prediction models trained primarily in breast tissue, and they did not account for alternative splicing of genes. Methods: In this study, we utilized two approaches to perform multi-tissue TWASs of breast cancer by ER subtype: (1) an expression-based TWAS that combined TWAS signals for each gene across multiple tissues and (2) a splicing-based TWAS that combined TWAS signals of all excised introns for each gene across tissues. To perform this TWAS, we utilized summary statistics for ER + BC from the Breast Cancer Association Consortium (BCAC) and for ER- BC from a meta-analysis of BCAC and the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). Results: In total, we identified 230 genes in 86 loci that were associated with ER + BC and 66 genes in 29 loci that were associated with ER- BC at a Bonferroni threshold of significance. Of these genes, 2 genes associated with ER + BC at the 1q21.1 locus were located at least 1 Mb from published GWAS hits. For several well-studied tumor suppressor genes such as TP53 and CHEK2 which have historically been thought to impact BC risk through rare, penetrant mutations, we discovered that common variants, which modulate gene expression, may additionally contribute to ER + or ER- etiology. Conclusions: Our study comprehensively examined how differences in common variation contribute to molecular differences between ER + and ER- BC and introduces a novel, splicing-based framework that can be used in future TWAS studies. [ABSTRACT FROM AUTHOR]

Background: Cell senescence is a sign of aging and plays a significant role in the pathogenesis of age-related disorders. For cell therapy, senescence may compromise the quality and efficacy of cells, posing potential safety risks. Mesenchymal stem cells (MSCs) are currently undergoing extensive research for cell therapy, thus necessitating the development of effective methods to evaluate senescence. Senescent MSCs exhibit distinctive morphology that can be used for detection. However, morphological assessment during MSC production is often subjective and uncertain. New tools are required for the reliable evaluation of senescent single cells on a large scale in live imaging of MSCs. Results: We have developed a successful morphology-based Cascade region-based convolution neural network (Cascade R-CNN) system for detecting senescent MSCs, which can automatically locate single cells of different sizes and shapes in multicellular images and assess their senescence state. Additionally, we tested the applicability of the Cascade R-CNN system for MSC senescence and examined the correlation between morphological changes with other senescence indicators. Conclusions: This deep learning has been applied for the first time to detect senescent MSCs, showing promising performance in both chronic and acute MSC senescence. The system can be a labor-saving and cost-effective option for screening MSC culture conditions and anti-aging drugs, as well as providing a powerful tool for non-invasive and real-time morphological image analysis integrated into cell production. [ABSTRACT FROM AUTHOR]

The substantia gelatinosa (SG) within the trigeminal subnucleus caudalis (Vc) is recognized as a pivotal site of integrating and modulating afferent fibers carrying orofacial nociceptive information. Although naringenin (4',5,7-thrihydroxyflavanone), a natural bioflavonoid, has been proven to possess various biological effects in the central nervous system (CNS), the activity of naringenin at the orofacial nociceptive site has not been reported yet. In this study, we explored the influence of naringenin on GABA response in SG neurons of Vc using whole-cell patch-clamp technique. The application of GABA in a bath induced two forms of GABA responses: slow and fast. Naringenin enhanced both amplitude and area under curve (AUC) of GABA-mediated responses in 57% (12/21) of tested neurons while decreasing both parameters in 33% (7/21) of neurons. The enhancing or suppressing effect of naringenin on GABA response have been observed, with enhancement occurring when the GABA response was slow, and suppression when it was fast. Furthermore, both the enhancement of slower GABA responses and the suppression of faster GABA responses by naringenin were concentration dependent. Interestingly, the nature of GABA response was also found to be sex-dependent. A majority of SG neurons from juvenile female mice exhibited slower GABA responses, whereas those from juvenile males predominantly displayed faster GABA responses. Taken together, this study indicates that naringenin plays a partial role in modulating orofacial nociception and may hold promise as a therapeutic target for treating orofacial pain, with effects that vary according to sex. [ABSTRACT FROM AUTHOR]

There is a lack of effective treatment options for diabetic refractory wounds, which presents a critical clinical issue that needs to be addressed urgently. Our research has demonstrated that human placenta-derived mesenchymal stem cells (plaMSCs) facilitate the migration and proliferation of HaCat cells, thereby enhancing diabetic wound healing primarily via the exosomes derived from plaMSCs (plaMSCs-Ex). Using label-free proteomics, plaMSCs and their exosomes were analysed for proteome taxonomic content in order to explore the underlying effective components mechanism of plaMSCs-Ex in diabetic wound healing. Differentially expressed proteins enriched in plaMSCs-Ex were identified and underwent bioinformatics analysis including GO annotation, KEGG pathway enrichment, gene set enrichment analysis (GSEA) and protein-protein interaction analysis (PPI). Results showed that the proteins enriched in plaMSCs-Ex are significantly involved in extracellular matrix organisation, epithelium morphogenesis, cell growth, adhesion, proliferation and angiogenesis. PPI analysis filtered 2 wound healing-related clusters characterised by hub proteins such as POSTN, FN1, SPARC, TIMP1, SERPINE1, LRP1 and multiple collagens. In brief, the exosomal proteins derived from plaMSCs reveal diverse functions of regeneration and tissue remodelling based on proteomics analysis and potentially play a role in diabetic wound healing., (© 2024 The Wound Healing Society.)

The current evidence provides support for the involvement of bone marrow mesenchymal stem cells (BMSCs) in the regulation of airway epithelial cells. However, a comprehensive understanding of the underlying biological mechanisms remains elusive. This study aimed to isolate and characterize BMSC-derived exosomes (BMSC-Exos) and epithelial cells (ECs) through primary culture. Subsequently, the impact of BMSC-Exos on ECs was assessed in vitro, and sequencing analysis was conducted to identify potential molecular mechanisms involved in these interactions. Finally, the efficacy of BMSC-Exos was evaluated in animal models in vivo. In this study, primary BMSCs and ECs were efficiently isolated and cultured, and high-purity Exos were obtained. Upon uptake of BMSC-Exos, ECs exhibited enhanced proliferation (p < .05), while migration showed no difference (p > .05). Notably, invasion demonstrated significant difference (p < .05). Sequencing analysis suggested that miR-21-5p may be the key molecule responsible for the effects of BMSC-Exos, potentially mediated through the MAPK or PI3k-Akt signaling pathway. The in vivo experiments showed that the presence of methacrylated gelatin (GelMA) loaded with BMSC-Exos in composite scaffold significantly enhanced epithelial crawling in the patches in comparison to the pure decellularized group. In conclusion, this scheme provides a solid theoretical foundation and novel insights for the research and clinical application of tracheal replacement in the field of tissue engineering., (© 2024 Wiley Periodicals LLC.)

Background: Globally, breast cancer, with diverse subtypes and prognoses, necessitates tailored therapies for enhanced survival rates. A key focus is glutamine metabolism, governed by select genes. This study explored genes associated with T cells and linked them to glutamine metabolism to construct a prognostic staging index for breast cancer patients for more precise medical treatment., Methods: Two frameworks, T-cell related genes (TRG) and glutamine metabolism (GM), stratified breast cancer patients. TRG analysis identified key genes via hdWGCNA and machine learning. T-cell communication and spatial transcriptomics emphasized TRG's clinical value. GM was defined using Cox analyses and the Lasso algorithm. Scores categorized patients as TRG&#95;high+GM&#95;high (HH), TRG&#95;high+GM&#95;low (HL), TRG&#95;low+GM&#95;high (LH), or TRG&#95;low+GM&#95;low (LL). Similarities between HL and LH birthed a "Mixed" class and the TRG&#95;GM classifier. This classifier illuminated gene variations, immune profiles, mutations, and drug responses., Results: Utilizing a composite of two distinct criteria, we devised a typification index termed TRG&#95;GM classifier, which exhibited robust prognostic potential for breast cancer patients. Our analysis elucidated distinct immunological attributes across the classifiers. Moreover, by scrutinizing the genetic variations across groups, we illuminated their unique genetic profiles. Insights into drug sensitivity further underscored avenues for tailored therapeutic interventions., Conclusion: Utilizing TRG and GM, a robust TRG&#95;GM classifier was developed, integrating clinical indicators to create an accurate predictive diagnostic map. Analysis of enrichment disparities, immune responses, and mutation patterns across different subtypes yields crucial subtype-specific characteristics essential for prognostic assessment, clinical decision-making, and personalized therapies. Further exploration is warranted into multiple fusions between metrics to uncover prognostic presentations across various dimensions., (© 2024 Wiley Periodicals LLC.)

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC., (© 2024 John Wiley & Sons Ltd.)

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Additionally, obese and postmenopausal women are at higher risk of all-cause and breast cancer-specific mortality compared with non-obese women with breast cancer. In this context, increased levels of estrogens, excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, adipocyte-derived adipokines, hypercholesterolemia, and excessive oxidative stress contribute to the development of breast cancer in obese women. Genetic evaluation is an integral part of diagnosis and treatment for patients with breast cancer. Despite trimodality therapy, the four-year cumulative incidence of regional recurrence is significantly higher. Axillary lymph nodes as well as primary lesions have diagnostic, prognostic, and therapeutic significance for the management of breast cancer. In clinical setting, because of the obese population primary lesions and enlarged lymph nodes could be less palpable, the diagnosis may be challenging due to misinterpretation of physical findings. Thereby, a nomogram has been created as the "Breast Imaging Reporting and Data System" (BI-RADS) to increase agreement and decision-making consistency between mammography and ultrasonography (USG) experts. Additionally, the "breast density classification system," "artificial intelligence risk scores," ligand-targeted receptor probes," "digital breast tomosynthesis," "diffusion-weighted imaging," "18F-fluoro-2-deoxy-D-glucose positron emission tomography," and "dynamic contrast-enhanced magnetic resonance imaging (MRI)" are important techniques for the earlier detection of breast cancers and to reduce false-positive results. A high concordance between estrogen receptor (ER) and progesterone receptor (PR) status evaluated in preoperative percutaneous core needle biopsy and surgical specimens is demonstrated. Breast cancer surgery has become increasingly conservative; however, mastectomy may be combined with any axillary procedures, such as sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection whenever is required. As a rule, SLNB-guided axillary dissection in breast cancer patients who have clinically axillary lymph node-positive to node-negative conversion following neoadjuvant chemotherapy is recommended, because lymphedema is the most debilitating complication after any axillary surgery. There is no clear consensus on the optimal treatment of occult breast cancer, which is much discussed today. Similarly, the current trend in metastatic breast cancer is that the main palliative treatment option is systemic therapy., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)