World journal of stem cells最新文献

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, are characterized by the progressive loss of neuronal function and structure, leading to severe morbidity and mortality. Current therapeutic approaches are ineffective at stopping or reversing disease progression. Stem cell therapy has emerged as a promising candidate in research and treatment. Mesenchymal stem cells (MSCs) are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential. MSCs can differentiate into neurons and glial cells, modulate immune responses, and reduce inflammation, and their exosomes can promote neural repair and regulate neuronal function; thus, MSCs offer unique advantages for treating neurodegenerative diseases. However, challenges remain in optimizing cell delivery methods, ensuring the long-term survival and integration of transplanted cells, and fully understanding their therapeutic effects. This article primarily outlines the functions of MSCs in neurodegenerative diseases, with the intention that further research will fully harness their potential and translate these findings into clinical applications, offering new hope for patients suffering from neurodegenerative diseases.

Mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue have promising potential in regenerative medicine. The regenerative capacity of MSCs depends on their successful migration and engraftment at the injured site. Several preclinical and clinical studies have reported that MSCs effectively treat cardiac dysfunction. However, significant obstacles to MSC homing include peripheral sequestration and low survival rates. MSC-secreted extracellular vesicles exhibit effects similar to those of MSCs, contributing to cellular proliferation, differentiation, and various paracrine functions. This review explores the molecular pathways and mechanisms by which MSCs and extracellular vesicles modulate cardiac injuries. Additionally, we discuss the challenges associated with MSC homing and various strategies to enhance the process.

Background: Glioblastoma multiforme (GBM) is the most aggressive and prevalent primary malignant brain tumor in adults, marked by poor prognosis and high invasiveness. Traditional GBM invasion assays, such as those involving mouse brain xenografts, are often time-consuming and limited in efficiency. In this context, stem cell-derived neural organoids (NOs) have emerged as advanced, three-dimensional, human-relevant platforms that mimic the cellular architecture and microenvironment of the human brain. These models provide novel opportunities to investigate glioblastoma stem cell invasion, a critical driver of tumor progression and therapeutic resistance.

Aim: To evaluate studies using stem cell-derived NOs to model glioblastoma migration/invasion, focusing on methodologies, applications and therapeutic implications.

Methods: We conducted a systematic review following PRISMA guidelines, searching PubMed and Scopus for studies published between March 2019 and March 2025 that investigated NOs in the context of glioblastoma invasion/migration. After screening 377 articles based on predefined inclusion and exclusion criteria, 10 original research articles were selected for analysis. Extracted data were categorized into four analytical domains: (1) Tumor model formation; (2) NO characteristics; (3) NO differentiation protocols; and (4) Invasion/migration assessment methodologies.

Results: The included studies exhibit significant methodological heterogeneity GBM model development, particularly regarding model type, cell source and culture conditions. Most studies (70%) used suspension cell models, while 30% employed spheroids, with most research focusing on patient-derived glioblastoma stem cells. NOs were predominantly generated from human induced pluripotent stem cells using both guided and unguided differentiation protocols. Confocal fluorescence microscopy was the primary method used for assessing invasion, revealing invasion depths of up to 300 μm. Organoid maturity and co-culture duration influenced results, while key factors for model optimization included tumor cell density, organoid age and extracellular matrix composition. Some studies also tested therapeutic strategies such as Zika virus and microRNA modulation. Collectively, findings support the utility of NOs as effective tools for studying GBM behavior and therapeutic responses in a humanized three-dimensional context.

Conclusion: Human NOs represent promising platforms for modeling glioblastoma invasion in a humanized three-dimensional environment. However, a limited number of studies and methodological heterogeneity hinder reproducibility. Protocol standardization is essential to enhance the translational application of these models.

Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment. Exosomes are considered to be a promising therapeutic agent carrier due to their advantages such as low immunogenicity and easy targeting. More researches and future developments are needed, although exosome-based therapies need further research and development before they can be translated into clinical applications. In this review, we aimed to discuss comparatively two main exosome sources as mesenchymal stem cell (MSC)-derived and macrophage-derived exosomes on pancreatic cancer in terms of the therapeutic potential, advantages, disadvantages and also other comprehensive details. In vitro, in vivo and clinical phase studies examining the therapeutic potential of MSC-derived and macrophage-derived exosomes in pancreatic cancer will be discussed. We strongly believe that this review will guide the new investigations related to exosome-based targeted therapy in pancreatic cancer. In the meantime, we aimed to provide an overview of ongoing research on MSC and macrophage exosome-based therapies, focusing on their role in cancer treatment, particularly for pancreatic cancer. By examining current findings, this review will provide a broad perspective on the therapeutic potential and limitations of exosomes.

Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus, which can lead to end-stage renal disease, and is an important cause of death in patients with systemic lupus erythematosus. Treatment options include glucocorticoids, immunosuppressive agents and the addition of biologics. Recently, the therapeutic role of mesenchymal stem cells (MSCs) in LN has received extensive attention worldwide. MSCs can suppress autoimmunity, alleviate proteinuria and restore renal function by modulating the functions of various immune cells and reducing the secretion of inflammatory cytokines. Several clinical trials have investigated MSC treatment in LN with promising but sometimes inconsistent outcomes. This review summarizes the sources of MSCs and mechanisms in immunoregulation. Furthermore, it examines clinical trials evaluating the efficacy, safety, and limitations of MSC therapy in LN. By highlighting advances and ongoing challenges, this review underscores the potential of MSCs for LN treatment. More large-scale randomized controlled trials are needed to support the effectiveness of this therapy and pave the way for personalized and combinatorial therapeutic approaches.

Bone marrow-derived mesenchymal stem cells (BMSCs) and adipose tissue-derived mesenchymal stem cells (ADSCs), two principal subtypes of mesenchymal stem cells with multilineage regenerative potential, have emerged as promising therapeutic strategies for various diseases. While BMSCs and ADSCs exhibit distinct functional profiles tailored to different therapeutic applications, emerging evidence suggests that ADSCs may be a more promising approach for treating ischemic pathologies, including myocardial infarction, ischemic stroke, and peripheral artery disease, in comparison with BMSCs. However, the precise molecular mechanisms by which ADSCs enhance the therapeutic outcomes in these diseases remain poorly understood. In this editorial, we comment on the article by Li et al, which systematically compares the therapeutic efficacy of ADSCs and BMSCs derived from the same elderly patients with coronary heart disease and explores the underlying mechanism from a metabolic perspective. This study proposes that the metabolite L-arginine in ADSCs isolated from elderly patients promotes angiogenesis and protects against apoptosis in a hypoxic and ischemic microenvironment, thereby enhancing myocardial repair following infarction. These findings not only highlight the metabolic plasticity of ADSCs but also position L-arginine as a pivotal therapeutic effector in coronary heart disease. Given the novel and crucial role of L-arginine in ischemic heart diseases, further exploration of L-arginine in ADSCs (particularly those derived from elderly individuals) is essential, including its roles in angiogenesis, cell death, and the potential therapeutic implications in other ischemic pathologies. Additionally, further investigation into additional metabolites in ADSCs is warranted to enhance the therapeutic potential of ADSCs in ischemic pathologies.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disease for which effective disease-modifying therapies are lacking. Mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising therapeutic approach due to their unique biological functions and favorable biocompatibility. This review systematically explores the mechanism of action of MSC-Exos in AD therapy, including the removal of β-amyloid via the delivery of degradative enzymes, modulation of neuroinflammation, and promotion of neural regeneration. Meanwhile, this paper summarizes recent advances in preclinical and clinical studies, and analyzes the challenges in production standardization, safety assessment, and long-term efficacy validation of exosome therapies. Finally, several innovative strategies are proposed to enhance the therapeutic potential of MSC-Exos, including exosome functionalization and targeting optimization, gene editing techniques. This aims to promote the translation of exosomes from basic research to clinical application.

Background: Knee osteoarthritis (KOA) is a leading cause of arthritis-related morbidity. Mesenchymal stem cells (MSCs), as living biopharmaceuticals, have emerged as a potential treatment option due to their anti-inflammatory and immunomodulatory properties.

Aim: To compare the safety and efficacy of allogenic MSCs (^AlloMSCs) vs autologous MSCs (^AutoMSCs) in treating KOA in clinical settings.

Methods: We conducted a systematic review and network meta-analysis to compare the safety and efficacy of ^AlloMSCs vs ^AutoMSCs in treating KOA. Our systematic search of four databases, including PubMed, Cochrane, Embase, and ClinicalTrials.gov, identified relevant randomized controlled trials (RCTs) reporting MSC-based treatment for KOA and reporting visual analog scale, Western Ontario and McMaster Universities Osteoarthritis scores, and adverse events. We assessed the methodological quality of the studies using the Cochrane Collaboration tool and calculated risk ratios (RRs) and weighted mean differences [with 95% confidence intervals (CIs)]. Our statistical analyses used the R-Studio network meta-packages (version 2023.12.0). The study protocol was pre-registered on the International Prospective Register of Systematic Reviews (ID: CRD42024590866).

Results: Nineteen RCTs involving 1216 patients with KOA met the inclusion criteria of the study. The network meta-analysis showed that ^AlloMSCs gave a significant reduction in visual analog scale scores by 14.91 points (95%CI: -24.52 to -5.30) vs 12.95 points with ^AutoMSCs (95%CI: -24.42 to -1.48). For Western Ontario and McMaster Universities Osteoarthritis score, ^AlloMSCs led to a significant reduction of 23.12 points (95%CI: -31.15 to -15.10) compared with 12.45 points using ^AutoMSCs (95%CI: -19.31 to -5.59), thus revealing a significant improvement with ^AlloMSCs (weighted mean difference: -10.62, 95%CI: -21.23 to -0.11). Additionally, ^AutoMSCs treatment showed a higher risk of joint-related adverse events (RR = 1.39, 95%CI: 1.07-1.79) compared with ^AlloMSCs (RR = 1.13, 95%CI: 1.01-1.25).

Conclusion: ^AlloMSCs may offer superior clinical outcomes with a lower risk of adverse events compared with ^AutoMSCs in the treatment of KOA. However, the need for further RCTs directly comparing the two MSC types is crucial to validate this data, underscoring the importance of our findings in this field.

Intervertebral disc degeneration (IDD) results from an imbalance within the intervertebral disc, leading to alterations in extracellular matrix composition, loss of nucleus pulposus cells, increased oxidative stress, and inflammatory cascade. While IDD naturally progresses with age, some factors such as mechanical trauma, lifestyle choices, and genetic abnormalities can elevate the risk of symptomatic disease progression. Current treatments, including pharmacological and surgical interventions, fail to halt disease progression or restore IDD function. Although biological therapies have been evaluated, their effectiveness in reversing long-term disc degeneration remains inconsistent. Mesenchymal stem cell-based therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations, ethical issues, etc. To date, mesenchymal stem cell-derived extracellular vesicles (EVs) have emerged as promising therapeutic agents for regeneration and anti-inflammation. Their therapeutic effects are attributed to several mechanisms, such as the induction of regenerative phenotype, apoptosis mitigation, and immunomodulation. In addition, the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration. Due to the problems in clinical use, however, the efficiency of the EVs should be overcome further by optimizing cell culture conditions, engineering them to deliver drugs and targeting molecules, etc.

Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms. Conventional treatment strategies, such as immunosuppressive drugs and anti-inflammatory therapies, often demonstrate limited efficacy and are associated with considerable side effects. Recently, mesenchymal stem cells (MSCs) have attracted growing interest as a promising therapeutic approach, owing to their immunomodulatory properties and ability to promote tissue repair. However, the direct application of MSCs faces several limitations, including the risk of immunogenicity and difficulties in large-scale production. In this context MSC-derived exosomes (MSC-Exos), nano-sized extracellular vesicles secreted by MSCs, have emerged as a compelling alternative to cell-based therapies. Enriched with proteins, lipids, and nucleic acids, these exosomes exhibit potent anti-inflammatory and immunomodulatory effects. Their primary mechanisms of action include enhancing the population of regulatory T cells, modulating macrophage polarization, and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. The therapeutic potential of MSC-Exos extends beyond individual conditions, encompassing a wide range of autoimmune diseases. For instance in Behçet's disease, they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration. Moreover, MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Through mechanisms such as inflammation suppression, vascular repair, and the restoration of immune homeostasis, MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy. This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases, with particular emphasis on their clinical potential in Behçet's disease, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.