Background Interstitial cystitis/bladder pain syndrome (IC/BPS) is a refractory urological disorder for which effective disease‐modifying treatments remain limited. This meta‐analysis evaluates the preclinical efficacy of stem cell interventions for IC/BPS and establishes an evidence‐based roadmap for clinical translation. Methods A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was performed (up to July 8, 2025). Risk of bias was appraised using the SYRCLE framework. Our outcomes focused on bladder histopathology, local inflammatory markers, urodynamic profiles, voiding patterns, and nociceptive behaviors. Results Eighteen studies (27 comparisons) evaluating interventions based on mesenchymal stem/stromal cells (MSCs) in rat models were included. Stem cell therapy significantly alleviated histopathological damage by reducing mast cell infiltration (SMD = −2.42), collagen deposition (SMD = −2.13), and apoptosis (SMD = −3.09), while suppressing proinflammatory cytokines (TNF‐α, IL‐6, IL‐1β). Functionally, interventions increased bladder capacity (SMD = 2.69), prolonged intercontraction intervals (SMD = 2.39), and markedly alleviated visceral pain (SMD = −3.19). Subgroup analyses identified human embryonic stem cell (hESC)‐derived multipotent mesenchymal stem cells (M‐MSCs) as the most extensively validated reference type, though other cell types exhibited phenotype‐specific potential. Furthermore, a dose of 1 × 10 6 cells/rat, localized bladder wall injection (BWI), and allogeneic sources were identified as the most favorable preclinical parameters among the evaluated studies. Conclusions Stem cell therapy—predominantly represented by MSCs—represents a promising candidate intervention with potential disease‐modifying properties for IC/BPS in preclinical models. To inform future trial designs, we suggest a preliminary, theoretically scaled human equivalent dose window of 2.0 × 10 7 to 5.0 × 10 7 cells, preferentially administered via localized BWI. By exploring optimal cellular parameters and translational barriers, this study provides an evidence‐based reference framework to guide the transition of stem cell therapy from bench to bedside.
Rare disease is a condition that affects a small fraction of the population. In most cases, it has a known genetic cause but could also be associated with other contributing factors. As the affected individuals may exhibit diverse symptoms due to the genetic and phenotypic heterogeneity, non‐ or misdiagnosis of rare diseases is common. Their low incidence and prevalence present an obstacle to developing new therapies despite a major unmet need with only a few treatment options available. This is particularly relevant to rare neurological disorders as there are major difficulties in studying the mechanisms of initiation and progression of the central nervous system (CNS) disorders. Recent advances in biotechnology, specifically the use of human induced pluripotent stem cells (iPSCs) for modeling diseases, have been instrumental in providing a flexible platform that not only reflects the effects of genetic disturbances on the development of CNS disorders but also is capable of providing insights into complex multifactorial disorders. Whether the human iPSCs are harvested from the affected individuals or using the gene‐editing tools on cells from healthy individuals, valuable models can now be made available for studying these orphan conditions. In this narrative review, we explore the benefits of using human iPSC models over the existing platforms of other primary cell lines and animal models for the disease modeling and drug discovery and discuss the limitations and future aspects of the iPSC use in the investigation of rare neurological disorders.
Background Nonobstructive azoospermia (NOA) is characterized by impaired spermatogenesis, yet the molecular mechanisms regulating spermatogonial stem cells (SSCs) in NOA remain unclear. Forkhead box protein P1 (FOXP1), a transcription factor implicated in cell proliferation and differentiation, may play a critical role in SSC function. Methods Testicular tissues from OA and NOA patients were examined for FOXP1 expression using reverse transcription‐polymerase chain reaction (RT‐PCR) and immunohistochemistry (IHC). Cell viability, proliferation, and apoptosis were assessed by CCK‐8, EdU, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The interaction between the FOXP1 and GSK3B promoter was analyzed via bioinformatics, chromatin immunoprecipitation, and luciferase reporter assays. Western blotting evaluated Wnt/β‐catenin pathway activation. The role of this pathway was further confirmed by LiCl treatment in FOXP1‐silenced SSCs. Results FOXP1 was downregulated in NOA samples displaying defective spermatogenesis. FOXP1 knockdown inhibited SSC viability and proliferation while promoting apoptosis. Mechanistically, FOXP1 bound directly to the GSK3B promoter, repressing its transcription. Silencing FOXP1 increased GSK3B expression and suppressed Wnt/β‐catenin signaling. Activation of Wnt/β‐catenin by LiCl reversed the detrimental effects of FOXP1 knockdown on SSCs. Conclusion FOXP1 positively regulates SSC proliferation and survival by transcriptionally repressing GSK3B and maintaining Wnt/β‐catenin signaling. These findings highlight that the FOXP1‐GSK3B‐Wnt/β‐catenin signaling axis plays an essential role in maintaining SSC homeostasis and spermatogenic function and provides novel mechanistic insights into the molecular pathogenesis of NOA.
Background Colorectal cancer (CRC) progression is heavily driven by epithelial–mesenchymal transition (EMT) and the acquisition of cancer stem cell (CSC) properties. Elucidating the specific molecular drivers and dynamic indicators underlying these processes is crucial for advancing CRC management. Methods The clinical significance and diagnostic value of fibrinogen alpha chain (FGA) were evaluated using TCGA data, immunohistochemistry (IHC), and paired pre‐ and postoperative serum samples. The biological functions of FGA were assessed in HCT116 cells through Transwell and 3D spheroid formation assays. Immunoprecipitation‐mass spectrometry (IP‐MS) and protein–protein interaction (PPI) network analyses were utilized to uncover the underlying molecular mechanisms. Results FGA mRNA and protein are significantly upregulated in CRC tissues, and preliminary data indicate elevated serum FGA in CRC patients. Clinically, aberrant FGA expression correlates with tumor histological type, lymphatic invasion, and poor survival outcomes. In vitro, FGA overexpression is associated with the downregulation of E‐cadherin, upregulation of mesenchymal markers (Vimentin, ZEB1, Snail), and increased cell migration and spheroid formation. Mechanistically, IP‐MS identified a potential PPI network wherein FGA associates with ubiquitin‐specific proteases (USP7, USP10) and the catenin complex (β‐catenin, p120‐catenin), suggesting a potential role in mediating pro‐stemness signaling. Conclusion These findings suggest that FGA may contribute to CRC plasticity by modulating EMT and stem‐like properties in vitro. Furthermore, its dynamic postoperative reduction warrants further investigation to determine its utility for non‐invasive tumor monitoring.
The corneal endothelium, located in the posterior layer of the cornea, is critical to the maintenance of corneal clarity. Due to the limited proliferative capacity of the corneal endothelium, cell loss or damage can affect visual health. The lack of healthy corneal donors worldwide limits corneal transplantation, which is still the most successful clinical treatment. Since stem cells possess self-renewal capacity and can differentiate into various cell types including corneal endothelial cells (CECs), they represent a promising candidate for regenerative medicine. Many methods have been developed to induce stem cells to differentiate into CECs, mainly including chemical induction, physical induction, and coculture with adult corneal cells such as lens epithelial cells and CECs. In this review, the structure, function and marker identification of CECs are firstly introduced. Then, the methods and research progress regarding the differentiation of multipotent stem cells (mesenchymal stem cells [MSCs]) and pluripotent stem cells (embryonic stem cells [ESCs] and induced pluripotent stem cells [iPSCs]) into CECs are reviewed in detail, and both in vivo and clinical applications of stem cell-derived CECs are discussed. Finally, the challenges in stem cell differentiation into CECs are summarized, and future development directions are suggested.
