Toll/IL-1R (TIR) domain proteins, as central signaling hubs in innate immunity, dynamically orchestrate inflammatory responses and immune processes within the tumor microenvironment (TME) by mediating both MyD88-dependent and TRIF-dependent pathways. This review systematically elaborates on the dual regulatory roles of the TIR superfamily-encompassing toll-like receptors (TLRs), IL-1 receptors (IL-1Rs), and adaptor proteins-in tumor immunity, including the facilitation of stemness maintenance in cancer stem cells (CSCs) and the inductive mechanisms driving the formation of an immunosuppressive TME. From the perspective of clinical translation, the combinatorial therapeutic strategy of TIR agonists/inhibitors with immune checkpoint inhibitors (ICIs) represents a novel paradigm: the synergistic effects among TIR agonists/inhibitors, advanced nanodelivery systems, and radiotherapy-responsive prodrug technology provide a potential approach to address challenges such as systemic toxicity and low targeted delivery efficiency. Looking forward, the continuous advancement and broader application of TIR protein targets in the field of precision cancer immunotherapy hold great promise for offering new hope in the fight against malignant tumors.

Mesenchymal stem cell (MSC)-derived exosomes revealed therapeutic ability, particularly in cancer treatment, by transferring bioactive molecules like miRNAs. Hypoxia, a common tumor condition, influences both tumor progression and MSC behavior. This review explores how hypoxic conditions affect MSC-derived exosomes and their impact on cancer-related pathways and genes.

Stem cell therapy has emerged as a potential regenerative approach for Acute myocardial infarction (AMI). Despite decades of research and advancement in acute myocardial infarction (AMI) management, translating innovative therapies from bench to bedside remains a central challenge. Nonetheless, clinical outcomes exhibit considerable variability. This review provides a comprehensive overview of the clinical landscape of stem cell therapy for AMI, specifically focusing on how variations in cell type, delivery timing, routes, and dosages can affect cell therapy efficacy.

Diabetes mellitus includes a wide range of chronic metabolic disorders that result in severe hyperglycemia and other damages in diabetic patients due to impaired insulin secretion or insulin inefficiency. This study purpose was to consider of the potential therapeutic properties of MSCs-derived EVs/Exo against DM. A complete systematic search was achieved in various electronic databases (Scopus, Web of Science, PubMed and Embase) up to June 2025, following the PRISMA guidelines. A whole of 89 studies were screened based on predetermined standards for inclusion and exclusion. Eventually, the current systematic study contained 13 publications that had the criteria of inclusion. According to the findings of this study, MSCs-derived EVs/Exo reduce DM and hyperglycemia with the high ability to regulate inflammatory-immune responses and activate autophagy pathways. However, compared to the diabetic groups, treatment with MSCs-derived EVs/Exo revealed tendency towards immunomodulatory, anti-inflammatory, anti-diabetic, regeneration and neogenesis of β-islets. In other studies, have been identified that DM causes significant biochemical changes in beta cells/pancreas tissue. In addition, obvious histological changes were observed in pancreatic tissue following DM. Generally, MSCs-derived EVs/Exo administration modulated most of the histological and biochemical changes caused by diabetes. Notably, the DM is improved through recovering damaged tissues, increasing insulin levels and glycemic stability. It seems that, MSCs-derived EVs/Exo exert these protective and therapeutic properties through the modulating of multiple mechanisms that are implicated in DM.

Background & objectivesThe impact of cell passaging and cryopreservation on the phenotypic and functional attributes of adipose-derived stem cells (ADSCs) must be understood to improve their clinical value. This systematic review investigates the phenotypic characteristics of ADSCs derived from fresh and cryopreserved adipose tissue, with a focus on how these cells change across passages. MethodsA thorough search of databases was conducted as per the PRISMA guideline to find publications that were aligned with the inclusion criteria and were published between January 2013 and January 2023. ResultsIn both cryopreserved and fresh stromal vascular fraction (SVF) cells, CD90, CD73, and CD105 consistently exhibited strong expression (90%) across passages in 50 screened studies. In fresh tissue, CD29 was upregulated in subsequent passages (up to 95%) but downregulated at passage 2 (2.3%). Variable CD29 was seen in cryopreserved groups (47% at P1, 90% at P4). While CD34 and CD45 were lower in cryopreserved ADSCs (less than 5%), they were higher in fresh tissue (41%), suggesting less haematopoietic contamination. Interpretation & conclusionsPassaging and cryopreservation protocols can help maintain the therapeutic potential of ADSCs, providing a reliable source of functional stem cells for regenerative utilization.

The incidence of hip osteoarthritis (OA) is increasing with the aging population, leading to interest in intra-articular orthobiologic injections to alleviate symptoms and potentially slow disease progression. This systematic review aims to evaluate the clinical outcomes associated with six orthobiologic therapies for hip OA: hyaluronic acid (HA), platelet-rich plasma (PRP), autologous cells therapy (ACT), microfragmented adipose tissue (MFAT), and bone marrow aspirate (BMA) and its concentration (BMAC).

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is a severe complication frequently occurring in preterm infants, often resulting in permanent neurological impairment and persistent functional deficits. Human umbilical cord-derived mesenchymal stem cells have shown significant promise as a therapeutic approach in neonatal brain injury due to their robust paracrine effects, multipotent differentiation potential, and minimal immunogenic properties. The protective roles of human umbilical cord mesenchymal stem cells (hUC-MSCs) involve multiple synergistic pathways, such as suppressing neuroinflammatory responses, inducing apoptotic processes, stimulating neurogenesis and angiogenesis, and enhancing blood-brain barrier integrity. Additionally, hUC-MSCs and their extracellular vesicles (EVs) confer protective benefits through the secretion and delivery of bioactive substances, including cytokines and microRNAs (miRNAs), which can alleviate brain damage and subsequently enhance motor and cognitive outcomes. Although further large-scale clinical investigations are required to validate their effectiveness, current preclinical and animal studies provide preliminary evidence affirming the safety profile and therapeutic efficacy of hUC-MSCs treatment as an innovative strategy for managing GMH-IVH. LITERATURE SEARCH STRATEGY: We conducted a systematic literature search to identify relevant publications. The primary databases were PubMed and Web of Science, with the search period extending through October 2025. The search combined the following keywords and, where applicable, MeSH terms: "Germinal matrix hemorrhage," "Intraventricular hemorrhage," "GMH-IVH," "White matter injury," "Hydrocephalus," "mesenchymal stem cells," "MSC," "umbilical cord," "mechanism," "therapy," "neuroprotection," and "clinical trials." We also searched ClinicalTrials.gov for ongoing or completed trials of MSCs for neonatal brain injury. The selection prioritized original research, high-quality reviews, and meta-analyses. After an initial title-and-abstract screening, full texts of potentially relevant articles were examined. Studies offering the most significant insight into the mechanisms of hUC-MSC therapy in GMH-IVH were chosen for in-depth discussion in this review.

Background/Objectives: Periodontal diseases are highly prevalent worldwide, causing progressive destruction of the alveolar bone and eventual tooth loss when not treated. Despite advances in conventional periodontal therapies, complete tissue regeneration remains limited. This review aims to evaluate the efficacy, safety, and clinical relevance of stem cell-based tissue engineering approaches for regeneration of periodontal bone lesions. Methods: Following PRISMA guidelines, a systematic search was conducted across multiple databases, resulting in the inclusion of 17 studies in humans that met predefined PICO criteria. The study protocol was registered on PROSPERO (CRD420251229271). These studies assessed various stem cell sources, including dental and bone marrow-derived cells among others, both on their own and in combination with scaffolds or growth factors. Results: Most studies reported favorable outcomes in terms of clinical attachment gain, radiographic bone fill, probing depth reduction, and implant stability. No major adverse effects were noted, indicating good safety. However, results varied based on cell type, culture protocols, and defect characteristics. Conclusions: Stem cell therapy shows strong potential for periodontal regeneration, with outcomes that may potentially surpass those of conventional methods in selected cases. Further standardization, cost reduction, and long-term clinical trials are essential to confirm these findings and support their integration into daily dental practice.

The short-term mortality rate of hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is relatively high, and the optimal therapeutic method for HBV-ACLF is still controversial. This study aimed to investigate the effects of different therapeutic methods on 90-day prognosis of HBV-ACLF patients.

Stroke ranks among the top global causes of death and disability, with hemorrhagic stroke accounting for 9%-27% of cases. In China, intracerebral hemorrhage (ICH) outpaces Western rates, driving adult mortality and disability. Aging populations and urbanization diversify stroke risk factors, yielding a 28-day ICH mortality rate up to 47% (Greenberg et al., 2022)-sharply higher than ischemic stroke's 3%-with ∼75% of survivors facing permanent neurological deficits. ICH imposes heavy burdens on individuals, families, and society. Current medical and surgical treatments struggle to enhance long-term outcomes, prompting exploration of neural stem cell (NSC) transplantation. This approach replaces lost neurons via differentiation while offering anti-inflammatory, anti-apoptotic, and neuroprotective benefits. This systematic review evaluates NSC sources, delivery routes, ICH models, therapeutic mechanisms, and early clinical trials, outlining recent progress and future directions for treating hemorrhagic stroke with NSC transplantation.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive and refractory orthopedic disorder characterized by deterioration of the subchondral bone microstructure and eventual femoral head collapse, leading to hip joint dysfunction. Current therapeutic strategies offer limited efficacy and fail to reverse the necrotic process, with approximately 70% of patients eventually requiring total hip arthroplasty. Therefore, developing novel treatments capable of halting disease progression and promoting bone repair is crucial for addressing this clinical challenge. Exosomes, bioactive nanovesicles that regulate apoptosis, angiogenesis, and inflammation, represent a promising regenerative modality. In particular, stem cell-derived exosomes are considered to play a key role in the treatment of SONFH by promoting osteogenesis and angiogenesis and modulating inflammatory responses. However, the efficacy and mechanisms underlying exosome-based therapy for SONFH have not been systematically evaluated. A comprehensive synthesis of current evidence is urgently needed to inform future clinical translation.

Endometrial injury is a common cause of menstrual changes, abortion, and even infertility in women, including intrauterine adhesions (Asherman’s syndrome) and a thin endometrium. Hysteroscopic surgery and drug treatment are currently the main treatment methods; however, their effect is not satisfactory. Increasingly, studies have demonstrated that mesenchymal stem cells (MSCs) may be a safe and promising option for treating endometrial injury. This study aimed to evaluate the efficacy of MSCs in an endometrial injury model.

Neurodevelopmental and neurodegenerative diseases involve critical abnormalities in pathogenesis. Even though there exists copious drugs and treatments, still a need for an effective model for absolute replication of disease pathophysiology and therapeutic drug discovery. This comprehensive systematic review amasses methods and approaches for developing neuronal models for neurological diseases using hPSCs/iPSCs. Abundant culturing methods, growth factors, modulators and toxins were utilised to induce the disease and were appraised. Research articles were traced from Google Scholar, PubMed/NIH, and Science Direct. Publications using hPSCs/iPSCs as differentiated neuronal disease models were screened using PRISMA guidelines, with designed inclusion and exclusion criteria. This protocol highlights the procedures for developing 2D and 3D neuronal models derived from hPSCs/iPSCs. 2D neuronal models include NPCs, NSCs, and neural rosettes, neurons, while 3D methods rely on embryoid bodies, neurospheres, spheroids and organoids due to the enhanced differentiation, survival and maturation of hPSCs/iPSCs. These processes include varied factors for culturing. Growth factors like GDNF, BDNF, cAMP, ascorbic acid, TGF-β, and Dual-SMAD inhibition. Post-analytical techniques like MEA, H&E, TEM, microscopy, immunoassays, and electrophysiology ensures the structural and functional endorsements. These models offer researchers a reliable platform to investigate the disease physiopathology and drug design for neurological disorders.

Radiation-induced xerostomia (RIX) is a frequent, debilitating complication of head and neck radiotherapy for cancer. Preclinical studies suggest that mesenchymal stem cells (MSCs) may protect and regenerate salivary glands, but clinical evidence remains fragmented. This study evaluates the safety and efficacy of MSC therapy for RIX patients.

Intrauterine Adhesions (IUA), including Asherman's Syndrome, are a significant cause of female infertility, while stem cell interventions emerge as a promising therapeutic strategy. This meta-analysis aims to systematically evaluate the effectiveness of stem cell interventions for IUA by analyzing various pregnancy outcomes.

Platelet-rich plasma (PRP) has emerged as a promising orthobiologic treatment for osteochondral lesions of the talus (OLTs), yet its clinical efficacy and mechanistic rationale remain under investigation.

Recent decades have witnessed a high prevalence of knee osteoarthritis among adults, which is associated with chronic pain, functional limitations, and decreased quality of life. Given the ineffectiveness of conventional cartilage regeneration approaches, umbilical cord-derived mesenchymal stem cells (UC-MSCs) have emerged as a potential regenerative therapy. In this study, it was aimed to determine whether UC-MSC treatment for knee osteoarthritis is effective, safe, and what is the optimal dosage to achieve optimal outcomes.

Thermogenic adipocytes present a promising therapeutic strategy for metabolic diseases. While murine models have provided valuable insights into thermogenic adipose tissue, their relevance to human physiology is constrained by species-specific differences in tissue distribution and thermogenic capacity. In vitro human models offer a more controlled platform to study adipocyte differentiation, addressing challenges such as limited access to deep fat depots and individual variability. This systematic review summarizes the current literature on human in vitro models for thermogenic adipocyte induction, encompassing 117 studies involving primary human adipocyte progenitors differentiated into thermogenic adipocytes in 2D cultures. Most studies relied on classical adipogenic inducers, including isomethylbutylxanthine, dexamethasone, and insulin, with additional use of triiodothyronine, rosiglitazone, or indomethacin. A few studies incorporated adrenergic stimulation or exposure to lower temperatures to simulate cold exposure. Notably, some studies demonstrated successful differentiation under serum-free, chemically defined conditions, highlighting their potential for reproducibility and translational relevance. A key limitation remains the predominant reliance on gene expression as the primary outcome, with few studies assessing mitochondrial respiration or broader metabolic functions. Moving forward, the development and adoption of standardized, functionally validated protocols will be critical to fully realize the potential of human in vitro thermogenic adipocyte models in metabolic research.

In recent years, the use of mesenchymal stem cells (MSCs), especially those derived from bone marrow and embryonic sources, has been considered as an emerging therapeutic approach for repairing joint tissue and reducing osteoarthritis symptoms. This systematic review and meta-analysis evaluated bone marrow-derived mesenchymal stem cells (BM-MSCs) efficacy, safety, and optimal dosing for osteoarthritis treatment.

Stem cell-based therapy, a crucial area of regenerative medicine, aims to enhance the body’s repair mechanisms by stimulating, modulating, and regulating endogenous stem cells or replenishing cell pools, thereby promoting tissue homeostasis and regeneration and offering promising treatments for numerous systemic diseases. This systematic review comprehensively summarizes animal studies investigating the efficacy of dental mesenchymal stem cells (DMSCs) in treating systemic diseases and promoting tissue regeneration compared to mesenchymal stem cells (MSCs) derived from other sources.