World journal of stem cells最新文献

Tendon-bone healing remains a significant clinical challenge due to the high risk of re-rupture following injury. While mesenchymal stem cells (MSCs) show great potential in enhancing tendon-bone healing, their clinical application is limited by issues such as low delivery efficiency, restricted differentiation potential, and potential immunogenicity. Recently, various strategies combining MSCs with other approaches, such as preconditioning, biomaterial integration, gene modification, and exosome application, have been developed, resulting in improved therapeutic outcomes. This review explored the current methods used to optimize MSC therapy for tendon-bone healing, examining the advantages, disadvantages, and underlying mechanisms of each approach, providing a foundation for future research and clinical applications.

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt disease, are primary contributors to irreversible vision loss globally. Due to the scarcity of effective curative treatments, stem cell therapy has emerged as a revolutionary advancement in ophthalmology. In the last ten years, significant advancements have been achieved in the derivation of retinal pigment epithelium and photoreceptor precursors from human embryonic stem cells and induced pluripotent stem cells, with initial clinical trials indicating safety and potential efficacy. Innovative delivery platforms, such as biodegradable scaffolds, microcarrier suspensions, and minimally invasive subretinal devices, are tackling prior challenges related to cell survival and integration. Simultaneously, gene-edited and patient-specific induced pluripotent stem cells are positioned to surmount immunological and ethical constraints. Future combinatorial strategies that incorporate stem cells with gene therapy, CRISPR-mediated editing, and bioengineered retinal organoids offer potential for personalized and regenerative methodologies. Nonetheless, enduring functional integration, immune tolerance, and oncogenic safety continue to pose significant challenges. To effectively transition from laboratory research to clinical application, collaborative frameworks among academic institutions, biotechnology companies, and regulatory agencies will be crucial for unlocking the complete therapeutic potential of stem cell-based treatments for retinal diseases. Stem cell therapy has transitioned from a distant promise to an advancing reality set to transform retinal care.

Breast cancer remains a leading cause of cancer-related death in women worldwide. Emerging evidence highlights the central roles of breast cancer stem cells (BCSCs) and circulating tumor cells (CTCs) in tumor initiation, progression, therapeutic resistance, and metastasis. BCSCs self-renew and drive intertumoral heterogeneity, while CTCs disseminate from primary tumors into the bloodstream, seeding distant sites. These populations share molecular features, including stemness and epithelial-mesenchymal transition markers, supporting the concept that a subset of CTCs acquires stem-like traits, enhancing metastatic potential and resistance to standard therapies. This review synthesizes current knowledge on BCSC molecular programs, key signaling pathways (e.g., Wnt, Notch, Hedgehog, Janus kinase/signal transducer and activator of transcription), and microenvironmental interactions that sustain stemness. It also examines mechanisms of CTC intravasation, state-dependent detection strategies, and their diagnostic and prognostic utility. We further highlight the adaptive plasticity of cancer stem cell-like CTCs, their contributions to drug resistance, and opportunities to target these phenotypes for personalized treatment. Clarifying the biological links between BCSCs and CTCs could enable earlier detection of hidden metastasis and inform combination therapies aimed at both stemness and dissemination. As multimodal detection improves and functional profiling matures, integrating BCSC/CTC analyses into routine care may refine risk stratification and guide individualized management.

Background: Irritable bowel syndrome (IBS) is a complex bowel disorder marked by recurrent abdominal pain and irregular stools. The condition is persistent and significantly affects the quality of life of patients. In China, 5.6%-11.5% of the population has IBS, with diarrheal IBS (IBS-D) comprising about 31.5% of the total.

Aim: To investigate how human umbilical cord mesenchymal stem cells (hUC-MSCs) can alleviate the symptoms with the help of an IBS-D rat model.

Methods: Sixty specific pathogen-free-grade male Sprague-Dawley rats were acquired and divided into five groups: Control group, model group, and three hUC-MSC groups with different doses. The model group was induced using a combination of acetic acid and binding stress. We determined the body weight of the mice; analyzed their fecal characteristics, inflammatory factors, and intestinal tissue damage; and conducted intestinal flora analyses.

Results: The results showed that hUC-MSCs observably restored the dramatic weight loss in the rat model and also lowered the fecal water content to some extent. In addition, hUC-MSCs reduced the expression of inflammatory factors to alleviate the inflammatory response and increased the expression of intestinal barrier functional proteins to restore the colon injury by colonizing the colon tissue. In addition, hUC-MSCs were able to maintain the abundance and diversity of gut flora.

Conclusion: Thus, hUC-MSCs can reduce the expression of inflammatory factors, improve the expression of intestinal barrier functional proteins, and maintain the abundance and diversity of intestinal flora in IBS-D by colonizing the colon tissue.

Background: Our mission is to cure hematopoietic malignancies through cell therapy. Time to transplant is a key challenge resulting in mortality of patients needing a transplant. Previous studies reported CD146+ mesenchymal stem cells (MSCs) regulating hematopoiesis in bone marrow (BM). In 2013, the study reported the existence in the synovium of a MSC subset, co-expressing CD73 and CD39, with greater osteo-chondrogenic potency and ability to produce adenosine. This subset expressed CD146, known to be associated with pericytes.

Aim: To investigate the presence and characterization of the CD73+CD39+CD146+ MSC subset in BM. Furthermore, we explored the existence of this subset in mobilized blood.

Methods: BM cells were culture expanded up to passage 4. Flow cytometry was used to verify expression of CD73, CD39, and CD146 markers. Cell sorting was performed via BDFACS AriaTM Fusion. The subset was assessed for defined MSC characteristics and perivascular localization in BM sections. Peripheral blood derived MSCs were obtained through apheresis performed at Gift of Life under Institutional Review Board donor consent.

Results: Our findings demonstrated that the combination of CD73, CD39, and CD146 enabled the identification and purification of a subset of MSCs from culture-expanded BM, up to passage 4. This subset exhibited a CD45-CD73+CD39+CD146+ phenotype, along with self-renewal and multipotency abilities, and was located in perivascular areas of BM sections. Additionally, this subset was found in both single and dual-mobilized leukopaks.

Conclusion: The CD73+CD39+CD146+ cell subset showed self-renewal and multipotency abilities and was located in perivascular areas of BM. Such cell subset was also reported in single and dual-mobilized leukopaks.

Background: Knee osteoarthritis (OA) is a degenerative joint disease traditionally viewed through the lens of cartilage degradation. However, emerging evidence positions subchondral bone pathology - particularly bone marrow lesions (BMLs) - as a key contributor to pain, progression, and structural deterioration. Mesenchymal stem cell exhaustion within the osteoarthritic subchondral zone further impairs intrinsic repair mechanisms, reinforcing the rationale for biologic interventions.

Aim: To evaluate the clinical efficacy of bone marrow aspirate concentrate (BMAC) therapy for knee OA, comparing subchondral vs intra-articular delivery routes, and elucidating the therapeutic impact on symptom relief and structural preservation.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, five clinical studies were included - comprising three randomized controlled trials and two prospective cohorts - with pooled data from 298 knees. Data on functional outcomes, imaging findings, and progression to total knee arthroplasty (TKA) were extracted and qualitatively synthesized.

Results: Subchondral BMAC injections demonstrated superior improvements compared to intra-articular injection or placebo: Knee Injury and Osteoarthritis Outcome Score improved from 49.1 ± 1.9 to 61.2 ± 6.3 at 12 months (P < 0.05), Knee Society Score increased from 57 ± 12 to 87.3 ± 12 at two years, and Western Ontario and McMaster Universities Arthritis Index scores showed significant improvement favoring combined approaches. Magnetic resonance imaging analyses revealed mean BML volume regression of 2.1 cm³, with 80% of knees avoiding TKA over 13-year follow-up. Magnetic resonance imaging analyses revealed regression of BMLs and increased cartilage preservation in subchondral-treated knees. Long-term data indicated delayed progression to TKA and biomechanical improvements (e.g., Hip-Knee-Ankle angle correction). No major adverse events were reported.

Conclusion: Targeting subchondral bone with BMAC addresses underlying OA pathology and may offer disease-modifying potential beyond symptom relief. These findings support a paradigm shift toward whole-joint biologic therapy, positioning the subchondral matrix as a therapeutic epicenter in OA management.

Background: Emerging evidence indicates that hypoxic preconditioning boosts the antioxidant and anti-apoptotic capacities of mesenchymal stem cell-derived exosomes; however, the specific mechanisms remain incompletely elucidated. This study explored the impact of hypoxia-preconditioned mesenchymal stem cell-derived exosomes (hypo-Exos) vs normoxic counterparts on the apoptotic response in cardiomyocytes triggered by oxidative stress.

Aim: To determine whether and how hypoxic preconditioning augments the cardioprotective efficacy of hypo-Exos against oxidative stress-induced cardiomyocyte apoptosis.

Methods: H9C2 cardiomyocytes were treated with hydrogen peroxide (H₂O₂) to induce oxidative injury. Assessments of cell viability, oxidative biomarkers, and apoptotic activity were conducted to evaluate the therapeutic efficacy of hypo-Exos and normoxic counterparts. High-throughput sequencing was performed to identify potential target microRNAs (miRNAs). Luciferase reporter assays were conducted to confirm selected miRNAs binding to target genes. Hypo-Exos loaded with selected miRNAs antagomirs or negative controls were administered to H₂O₂-treated H9C2 cells to validate the downstream signaling pathways involved.

Results: Hypo-Exos significantly enhanced cell viability, reduced oxidative stress, and inhibited apoptosis of cardiomyocytes. Hypoxic preconditioning significantly increased the expression of exosomal miR-486-5p, which directly targeted the phosphatase and tensin homolog. Additionally, hypo-Exos markedly activated the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Moreover, deletion of miR-486-5p in hypo-Exos counteracted the anti-apoptotic effects and suppressed PI3K/Akt pathway activation.

Conclusion: Hypoxic preconditioning augments anti-apoptotic properties of exosomes, primarily via miR-486-5p upregulation, which mediates its function by modulating the phosphatase and tensin homolog/PI3K/Akt axis.

Background: The discovery of induced pluripotent stem cells revolutionized regenerative medicine, providing a source for generating induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs).

Aim: To evaluate and compare five iMSC differentiation protocols, assessing their efficiency, phenotypic characteristics, and functional properties relative to primary mesenchymal stem cells (MSCs).

Methods: Five iMSC differentiation protocols were assessed: SB431542-based differentiation (iMSC1, iMSC3), an iMatrix-free method (iMSC2), growth factor supplementation (iMSC4), and embryoid body formation with retinoic acid (EB-iMSC). iMSC identity was confirmed according to the International Society for Cell & Gene Therapy 2006 criteria, requiring expression of surface markers (CD105, CD73, CD90) and absence of pluripotency markers. Functional assays were conducted to evaluate differentiation potential (osteogenic and adipogenic), proliferation, mitochondrial function, reactive oxygen species, senescence, and migration.

Results: All iMSC types expressed MSC markers and lacked pluripotency markers. EB-iMSC and iMSC2 showed enhanced osteogenesis (runt-related transcription factor 2; P ≤ 0.01 and P ≤ 0.0001, respectively), while adipogenic potential was reduced in iMSC2 (Adipsin; P ≤ 0.01) and EB-iMSC (Adipsin and peroxisome proliferator-activated receptor gamma; P ≤ 0.0001 and P ≤ 0.01, respectively). Proliferation was comparable or superior to bone marrow MSCs, except in iMSC1, with iMSC4 showing the highest rate (MTT assay; P values ranged from 0.01 to 0.001). Despite reduced mitochondrial health in iMSC3 and iMSC4 (P ≤ 0.001), reactive oxygen species levels were lower in all iMSCs (P values ranged from 0.001 to 0.0001), and senescence was significantly reduced in all iMSCs with the exception of iMSC1 (P values ranged from 0.01 to 0.0001). Migration was most reduced in iMSC4 (P ≤ 0.001 at 24 hours and P ≤ 0.0001 at 48 hours).

Conclusion: While all protocols generated functional iMSCs, variations in differentiation, proliferation, and function emphasize the impact of protocol selection. These findings contribute to optimizing iMSC generation for research and clinical applications.

Reflecting on 16 years of continuous evolution at the World Journal of Stem Cells, this editorial offers a forward-looking vision for redefining the framework of scientific publishing. With the emergence of artificial intelligence, open science, and the growing need for translational value, we propose shifting from traditional citation-based assessments toward an impact and progress framework, anchored by the Economic Impact Factor. The World Journal of Stem Cells experience, grounded in metrics and milestones, supports this evolution: Among the more than 1200 published articles since inception, our top 10 cited works have collectively accrued over 2475 citations, led by Kyurkchiev et al (398 citations) and Casteilla et al (392 citations). Emerging scholars such as Ann De Becker and Nipha Chaicharoenaudomrung have shaped the next generation of research, as seen in our top 10 junior authors table. Clinically, World Journal of Stem Cells has supported critical translational work, such as Tsang et al's mesenchymal stem cell stroke trial (27 citations), illustrating real-world impact. Thematic breadth remains a cornerstone, with 22 focus areas including artificial intelligence-integrated programming, spatial single-cell biology, CRISPR-based gene editing, and bench-to-bedside translation. As Nature and other leading publishers move toward transparent peer review, World Journal of Stem Cells embraces editorial co-creation, recognizing peer reviewers and editors as contributors with "10000-foot eagle views" by publishing peer-review reports side-by-side with the related manuscripts since its inception. Together, these shifts signify a call to recalibrate what we value in science - not just what is cited, but what truly counts.

Mesenchymal stem or stromal cells (MSCs) are among the most extensively studied cell populations in regenerative medicine due to their multipotent differentiation potential, secretion of trophic factors, and immunomodulatory effects. Over the past two decades, preclinical studies have demonstrated encouraging results across musculoskeletal, cardiovascular, neurological, and immune-mediated disorders. However, the translation of MSCs from the laboratory to routine clinical practice remains hindered by unresolved scientific, technical, and regulatory challenges. This review provides a critical appraisal of these hurdles, organized across three major stages of translation: In vitro research, in vivo animal studies, and clinical application. In vitro issues include the heterogeneity of isolation techniques, replicative senescence during expansion, genetic and epigenetic instability, and the need for xeno-free, standardized culture platforms. In vivo challenges arise from poor cell survival, low engraftment rates, off-target migration, and microenvironmental influences that shape therapeutic outcomes. Clinical translation introduces additional complexity, including inter-patient variability, large-scale manufacturing difficulties, stringent regulatory compliance, high production costs, and the absence of harmonized potency assays. Solutions under exploration include the use of automated bioreactors, biomimetic scaffolds, hypoxic preconditioning, extracellular vesicle-based therapies, and international standardization efforts. Addressing these hurdles through multidisciplinary collaboration is essential for MSC-based therapies to become reliable, safe, and accessible regenerative treatments.