Hematopoietic stem cell transplantation (HSCT) is a cornerstone in the treatment of hematological disorders. However, its application is frequently complicated by acute and chronic graft-versus-host disease (aGVHD/cGVHD), pathological conditions in which donor-derived immune cells attack host tissues. With suboptimal survival rates and limited therapeutic options, GVHD remains a major clinical challenge. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality due to their immunomodulatory capabilities, yet standardized protocols for their use in preventing or treating GVHD have not been established.

Organoids are mini-organs engineered to mimic the native tissue's organization, cellular structure, and function. Lacrimal gland organoids are considered a potential treatment for patients with dry eye, but the gland's complex heterogeneity has been difficult to replicate. This systematic review summarizes methods for creating lacrimal gland organoids, their characterization, and potential applications. Data collected included organoid source, composition of expansion or differentiation media, biomarkers, gene expression, responses to stimulants, and effects in animal models. The sources of lacrimal gland organoids were human induced pluripotent stem (hiPS) cell lines (n = 2) and tissue biopsies from humans, mice, or pigs (n = 5). Tissue-derived organoids from mice grew for 40 passages, while those from human biopsies lasted up to 20 passages. There is a need to optimize the culture protocol to preserve cell composition and support long-term growth. The organoids expressed epithelial markers (KRT5, KRT13, AQP), mesenchymal markers (Vimentin and α-SMA), and developmental markers (PAX6, TP63, and OCT3/4), though cellular proportions varied between studies. Stimulation studies showed increased calcium influx and β-glucosaminidase activity, indicating secretory capacity. RNA sequencing revealed unique gene expression patterns associated with stemness and functional maturity, including tear proteins and markers of ductal and myoepithelial cells. PAX6 knockout studies confirmed PAX6's essential role in organoid growth. Published studies lack data on epithelial polarity, the coexistence of ductal and acinar cells within organoids, and the in vivo secretory function of organoids. Transplanted organoids into animal models of dry eye disease (two immunosuppressed and two naïve) remained viable for 8 weeks and expressed tear-related markers (AQP5, KRT14, PAX6), although there was no data on tear film or ocular surface changes. Future research could explore the effects of transplantation on the ocular surface and host immune responses.

Astrocytes are increasingly recognized as dynamic regulators of synaptic, metabolic, vascular, and immune functions in the brain, far beyond their long-assumed supportive role. While adult neurogenesis has been extensively studied, adult astrogliogenesis, the generation of new astrocytes from neural stem cells, the proliferation of mature astrocytes, or the differentiation of oligodendrocyte progenitor cells, remains comparatively underexplored. Emerging evidence indicates that adult astrogliogenesis plays a vital role in maintaining brain homeostasis, responding to injury, and modulating disease progression, with potential therapeutic relevance in neurological and psychiatric disorders. This systematic review followed PRISMA 2020 guidelines and screened 4512 records published between June 2020 and June 2025 across multiple databases, with 17 studies meeting all eligibility criteria. Findings reveal that adult astrogliogenesis occurs under both physiological and pathological conditions, exhibiting notable heterogeneity in origin, regulation, and function. In healthy brains, astrocyte generation is relatively limited, confined mainly to canonical neurogenic niches, the subventricular zone and the hippocampal dentate gyrus, and occurs primarily through local proliferation of mature astrocytes rather than neural stem cell differentiation. Under pathological conditions, astrogliogenesis is consistently upregulated, though outcomes vary across diseases and brain regions. Neurodegenerative disorders, such as Parkinson's and Huntington's diseases, display distinct proliferation patterns between the subventricular zone and the dentate gyrus. In inflammatory conditions, neural stem cell fate shifts toward astrocyte production, often at the expense of neurogenesis. Cerebrovascular injury triggers robust astrocytic proliferation, leading to the formation of protective borders and glial scars. Metabolic disturbances impair proliferation and cognitive function, linking iron homeostasis to astrocyte plasticity. Across all contexts, a key limitation lies in the absence of standardized markers to unequivocally identify newly generated astrocytes and determine their cellular origin. Most studies rely on co-labeling of proliferative and astrocytic markers, which indicate cell division but not lineage derivation. Accurate origin tracing requires genetic fate-mapping approaches, which remain rarely employed in current literature. Overall, adult astrogliogenesis emerges as a dynamic, context-dependent process that can either promote repair or exacerbate pathology. Under homeostatic conditions, stimuli such as deep brain stimulation or exercise may enhance or restore astrogliogenesis. In pathological contexts, proliferation is frequently amplified and accompanied by phenotypic shifts toward reactive states. Understanding these mechanisms could inform therapeutic strategies aimed at modulating astrocyte production to enhance beneficial repair while minimizing detrimental gliosis. Achieving this will require standardized methodologies, precise lineage tracing, and comprehensive mapping of astrocyte subpopulation functions across brain regions.

Oral potentially malignant disorders (OPMDs) have varying risk of malignant transformation (MT), yet the underlying mechanisms remain unclear. Recent evidence suggest emerging role of stem cells in carcinogenesis. This systematic review aimed to synthesizes current knowledge on the role of stem cells in OPMD and MT. Review protocol was developed in accordance with PRISMA 2020 guidelines and registered with PROSPERO. Literature searches identified 4882 records from PubMed, Scopus, Embase, and Web of Science databases; from these, n = 97 primary research studies were selected via two stage screening. Data extraction and narrative synthesis was conducted according to synthesis without meta-analysis (SWiM) guidelines. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal checklists. Studies included in this review were published between 2006-2025, where majority of the research were from India and China. Immunohistochemistry (IHC) was used to identify stem cell biomarkers in tissue samples, most studies demonstrated that higher expression of stem cell markers (CD44, ALDH1, HELLS, TARIF, SOX2, NANOG, and CD147) correlated with severity of epithelial dysplasia. Longitudinal data identified ALDH1 and Bmi-1 as promising prognostic biomarkers linked to MT. Evidence from cell culture and animal model experiments suggested potential therapeutic applications of stem cells and their exosomes in haltering the progression of OPMD. Notably, a clinical trial incorporated stem cell markers as surrogate end points for evaluating treatment options. While findings underscore the prognostic and therapeutic relevance of stem cells in OPMD, lack of prospective designs in biomarker validation and absence of clinical trial evidence on stem cell therapies limit clinical applicability.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that targets pancreatic beta cells, causing insulin deficiency and hyperglycemia. Unfortunately, till now, no conclusive treatment has been established for the entire treatment of T1DM. Today, Mesenchymal stem cells (MSCs) are widely used in regenerative medicine. MSCs have several advantages, including easy access, strong proliferation ability, differentiation power, minimal risk of tumorigenesis, and low risk of immunogenicity. However, there have been few clinical trials using MSC implants to treat T1DM. In this paper, we look at clinical trials using MSCs to treat T1DM and analyze the benefits and limitations of this approach. To collect crucial data, a comprehensive search was undertaken on articles published between 2015 and 2024. The search involved PubMed, Google Scholar, Embase, CINAHL, PsycInfo, and Cochrane databases. All MeSH words related to mesenchymal stem cells, clinical trials, and type 1 diabetes mellitus were searched. Relevant studies with full access, authored in English from 2015 to 2024, were selected. Ultimately, eleven papers that met the predetermined criteria underwent a comprehensive analysis. This systematic review reveals that MSC treatment is an acceptable treatment option for T1DM, with a positive safety profile observed in the evaluated research. The analyzed findings suggest potential benefits in sustaining beta-cell function and modifying the immunological response, which could lead to a decrease in insulin requirement. However, it remains to be proven as an alternative for insulin administration, and more detailed clinical research is necessary to verify its enduring effectiveness and reliability.

Treatment with umbilical cord blood (UCB) for cerebral palsy (CP) remains promising but experimental and unproven. An updated meta-analysis is needed to assess the efficacy of UCB mononuclear cells (MNCs) in comparison to UCB-derived mesenchymal stromal cells (MSCs) to clarify future directions in the use of UCB to treat CP. An updated systematic review of published controlled clinical trials to November 2024 was conducted and identified ten trials (621 patients; 71% of all patients from 7 trials received UCB-MNCs). Three trials administered UCB-MSCs (30%) and one study compared UCB-MNCs to UCB-MSCs. In one study, MNCs were administered with or without erythropoietin. Eight studies (80%) administered allogeneic cells. Dosage and route of cell administration varied. Clinical outcome reporting was variable, but allowed for meta-analysis of change in GMFM motor scores at 12 months (included 9 groups across 7 studies). Using a random effects model, the standardized mean difference in GMFM scores between baseline and 12 months was higher in the intervention group compared to controls (M= 0.5828, 95% CI=[0.19,0.98], P-value= 0.004). Subgroup analysis using a random-effects model revealed no statistically significant difference in GMFM scores from baseline to 12 months compared to controls in the MNC group (MA = 0.3225, 95% CI = [-0.19, 0.84], P -value= 0.22), whereas in the MSC group, GMFM scores improved more significantly compared to controls (MB = 0.9192, 95% CI = [0.33,1.50], P-value = 0.002). In conclusion, infusion of UCB-MSCs appears promising, with improved GMFM scores at 12 months for patients with cerebral palsy. Larger randomized controlled trials that examine MSCs derived from cord blood and other tissues appears worthwhile. Longer follow-up addressing the breadth of relevant clinical outcomes in CP are needed to confirm potential benefits for patients with CP.

Exosomes are secreted tiny organelles that are single-membrane enclosed and can perform a broad spectrum of functions upon release, such as the reorganization of extracellular matrix and communication with other cells through the release of signals and chemicals, which play an important role in development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases, among other aspects of human health and disease. This systematic review aimed to evaluate the clinical efficacy and safety of exosome-based therapies for skin rejuvenation in human populations and to identify gaps in the existing evidence. A methodological literature search was performed in databases such as PubMed, Scopus, Cochrane Library, and Web of Science with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Clinical experiments that were conducted on humans to assess exosome-based interventions to rejuvenate the aesthetic skin were encompassed. The process of study selection, data extraction, and quality appraisal was done independently by two reviewers. Synthesis of results was narrative, since there was methodological heterogeneity. A total of 19 studies were included, but most of them were not randomized. There was an association between exosome-based interventions and skin hydration, elasticity, wrinkles, pores, pigmentation, and overall appearance improvement in the short term. The majority of the studies reported a positive safety profile of topical application, with the exception of individual reports of risks with off-label injectable use. Exosome-based therapies showed encouraging early clinical effects of skin rejuvenation, and the existing evidence is marred by heterogeneity and lack of follow-up. Rigorous randomized trials and standardized reporting are required.

Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients' quality of life, and effective treatments remain limited. As the focus is on treating the symptoms, the root cause of the problem is commonly not addressed. Mesenchymal stem cells show an emerging potential due to the ability for self-renewal combined with their capability for differentiation into various cell lines, which makes them a strong candidate for regenerative therapies in general, and for application in neurological issues in particular. This article provides an overview of the safety, efficacy, and challenges associated with the use of mesenchymal stem cells (MSCs) and their derived secretome in clinical and preclinical models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Methods: A systematic search was conducted on PubMed to identify published studies providing clinical and preclinical evidence on the use of MSCs in neurodegenerative disorders. Results: Overall, the literature consistently indicates that MSCs and their derivatives exert disease-modifying effects across multiple NDs. Across AD, PD, HD and ALS, preclinical studies uniformly report improvements in behavioural outcomes, attenuation of neuroinflammation, and neuroprotective effects, largely mediated by MSCs' paracrine signalling rather than direct cell replacement. Clinical studies to date consistently support the safety and feasibility of MSC-based therapies, while efficacy signals remain modest, heterogeneous and predominantly short-term, highlighting the need for larger, well-controlled trials. Conclusions: Integration of genetic engineering, preconditioning, and EV technology may represent an emerging therapeutic approach that may complement existing neuroregeneration treatments, offering a scalable and minimally invasive frontier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS.

Temporomandibular joint (TMJ) disorders represent chronic degenerative musculoskeletal conditions with a high prevalence in the general population and limited regenerative treatment options. Owing to the insufficient efficacy of current conservative and surgical therapies, there is a growing clinical need for biologically based regenerative approaches. Tissue engineering (TE), particularly scaffold-based strategies, has emerged as a promising avenue for TMJ regeneration. This systematic review analyzed preclinical in vivo studies investigating scaffold-based interventions for TMJ disc and osteochondral repair. A structured literature search of PubMed and Scopus databases identified 39 eligible studies. Extracted data included scaffold composition, use of cellular and bioactive components, animal models, and reported histological, radiological, and functional outcomes. Natural scaffolds, such as decellularized extracellular matrix and collagen-based hydrogels, demonstrated favorable biocompatibility and support for fibrocartilaginous regeneration, whereas synthetic materials including polycaprolactone, poly (lactic-co-glycolic acid), and polyvinyl alcohol provided superior mechanical stability and structural tunability. Cells were used in 17/39 studies (43%); quantitative improvements were variably reported across these studies. Bioactive molecule delivery, including transforming growth factor-β, histatin-1, and platelet-rich plasma, further enhanced tissue regeneration, while emerging drug- and gene-delivery approaches showed potential for modulating local inflammation. Despite encouraging results, the reviewed studies exhibited substantial heterogeneity in experimental design, outcome measures, and animal models, limiting direct comparison and translational interpretation. Scaffold-based approaches show preclinical promise but heterogeneity in design and incomplete quantitative reporting limit definitive conclusions. Future research should emphasize standardized methodologies, long-term functional evaluation, and the use of clinically relevant large-animal models to facilitate translation toward clinical application. However, functional and biomechanical outcomes were inconsistently reported and rarely standardized, preventing robust conclusions regarding the relationship between structural regeneration and restoration of TMJ function.

Cell-based therapy is a promising approach for ischemic stroke treatment. This systematic review and meta-analysis aimed to consolidate clinical evidence on the use of neuroimaging to evaluate stem cell therapy across all stages of stroke recovery.

Exosomes derived from dental stem cells (DSC-Exos) are nanovesicles (~ 30–150 nm) that mediate angiogenesis, odontoblastic differentiation, and immune regulation, positioning them as promising cell-free candidates for pulp–dentin regeneration. This PROSPERO-registered systematic review evaluated the regenerative potential of DSC-Exos and the methodological factors influencing outcomes. A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted through July 2025; risk of bias was assessed using RoB 2.0, SYRCLE, and QUIN tools. Thirteen studies fulfilled the inclusion criteria, most of which employed exosomes derived from human dental pulp stem cells, stem cells from human exfoliated deciduous teeth and stem cells from the apical papilla. DSC-Exos consistently promoted cell proliferation and migration while upregulating odontogenic (DSPP, DMP1) and angiogenic (VEGF, CD31) markers. Animal models demonstrated vascularized pulp-like tissue and organized tubular dentin formation, significantly enhanced by donor-cell preconditioning and biodegradable carriers. Mechanistic investigations linked these outcomes to noncoding RNAs and signaling axes like miR-26a/TGF-β and circ_0003057/EIF4A3/ANKH. A 24-month clinical pilot confirmed restored pulp sensitivity without safety concerns. Nevertheless, the overall certainty of evidence remains moderate to low, mainly due to substantial methodological heterogeneity, limited sample sizes and insufficient reporting of critical parameters such as exosome characterization, dosing strategies and operator calibration. Collectively, the findings indicate that DSC-Exos represent a high-potential biomimetic strategy for pulp–dentin regeneration; however, standardized characterization protocols in line with MISEV guidelines, dose harmonization and well-designed long-term controlled clinical trials are essential before cell-free endodontic therapies can be reliably incorporated into clinical practice.

To update the ASCO guideline on use of hematopoietic colony-stimulating factors (CSFs) in patients with cancer.

Cell therapy is a vital field in modern medicine. This review assesses its global clinical development landscape, approved products, and regional regulatory characteristics.

Three-dimensional (3D) bioprinting is a revolutionary technology in tissue engineering, particularly promising for oral tissues regeneration due to its capability to achieve precise spatial distribution and construct complex multiphase structures. This review provides a comprehensive overview of recent progress in the application of 3D bioprinting within the realm of oral tissue regeneration. The fundamental concepts of 3D bioprinting and its unique advantages in the context of oral tissue engineering are introduced at first. Subsequently, recent pivotal research findings and applications in the regeneration of periodontal tissues, dentin-pulp complex, craniomaxillofacial tissues, oral mucosa and salivary gland via utilizing 3D bioprinting techniques are summarized. At the end of this review, the clinical translational challenges, including bioprinting and tissue engineering technology bottlenecks as well as regulatory and ethical review deficiency are discussed. Potential strategy are offered thereafter. Overall, 3D bioprinting holds significant potential in oral regenerative medicine, and this review will provide significant cues for inspiring related innovative research, involving the investigation of underlying mechanisms, optimization of bioinks and printing parameters, which is conducive to propelling the clinical translation of this innovative technology.

This meta-analysis aimed to determine the effects of intra-articular mesenchymal stem cell (MSC)-based injections on both subjective and objective measures of pain and function in patients with knee osteoarthritis (OA). The secondary purpose was to investigate how injection procedures, patient characteristics and post-injection rehabilitation influence outcomes.

Tissue-engineering strategies combining mesenchymal stem cells (MSCs) or extracellular vesicles (EVs) with bone-regenerative scaffolds may improve healing of critical-size bone defects, yet their comparative efficacy remains unclear. We systematically searched PubMed, Embase, Scopus, Web of Science, and ProQuest for animal studies published up to July 1, 2025. Risk of bias was assessed using the SYRCLE tool. New bone formation was synthesized as bone volume/total volume (BV/TV) using conventional meta-analysis and Bayesian network fixed/random-effects models, reported as standardized mean difference (SMD) with 95% confidence interval (CI)/credible interval (CrI). Subgroup analyses were conducted by MSC source, EV use, scaffold type, anatomical site, and follow-up duration, with sensitivity analyses and assessment of publication bias. In total, 207 studies across 7 animal models were included. MSC-loaded scaffolds significantly enhanced bone regeneration compared with no treatment or scaffold alone, showing a strong short-term effect and consistent benefits at medium and long follow-up. Bone marrow MSC (BMSC)-laden scaffolds underperformed adipose-derived MSC (ADSC)-laden scaffolds, and BMSC-derived EVs further improved outcomes compared with cell-free scaffolds. Calvarial defect models demonstrated greater gains than long-bone models. Network meta-analysis suggested multi-component composite scaffolds had the highest potential for new bone formation among cell-free designs. Overall, MSCs/EVs combined with supportive scaffolds markedly increase bone regeneration in preclinical models, but heterogeneity in models, biomaterials, dosing, and outcome reporting limits direct clinical translation, underscoring the need for standardized protocols and core outcome sets. STATEMENT OF SIGNIFICANCE: This comprehensive meta-analysis incorporated network comparisons across diverse mesenchymal stem cells (MSCs) or extracellular vesicles (EVs) sources and biomaterial categories. It reveals that MSC-EVs, particularly when combined with scaffolds or hydrogels, are the most effective in improving BV/TV ratio (bone volume/total volume) and histological outcomes in animal bone defect models. These data indicate that MSC or EV-enhanced biomaterial strategies may be leading candidates for repairing critical-sized defects and provide a standardized roadmap for transitioning preclinical success into clinical practice.

Stroke is one of the most common causes of death and permanent neurological disabilities worldwide yet neuroprotective or regenerative therapies do not exist. Genetically modified neural stem cells (NSC) could help overcome key limitations of naïve or unmodified NSCs and improve therapeutic efficacy. The aim of this systematic review and meta-analysis is to evaluate existing preclinical literature using animal models to compare the therapeutic effects of genetically modified NSCs for stroke compared to naïve NSCs or vehicle control.

Bone healing following pathology or surgery is a complex, multiphase process involving coordinated cellular and molecular activities. Various stimulation strategies have been used to enhance bone repair. Recently, stromal vascular fraction (SVF)-a heterogeneous, adipose-derived cell mixture containing pericytes, smooth muscle cells, and adipose-derived stem cells with regenerative, immunomodulatory, and angiogenic properties-has been explored in clinical settings to promote accelerated bone regeneration.

Spinal cord injury (SCI) is a debilitating condition characterized by primary mechanical trauma followed by secondary neuroinflammation. Neural stem cells (NSCs) hold promise for SCI repair through their regenerative and immunomodulatory properties, including the promotion of anti-inflammatory macrophage phenotypes. However, the specific mechanisms by which NSCs modulate inflammation in preclinical models remain heterogeneous. This systematic review synthesizes evidence from rodent studies to elucidate these mechanisms and inform translational strategies. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025, using terms related to SCI, inflammation, and NSC transplantation. Preclinical studies involving NSC interventions in rodent SCI models were included if they assessed inflammatory outcomes. Data extraction focused on study characteristics, NSC administration, inflammation markers (e.g., cytokines, macrophage polarization), and functional recovery. Quality assessment followed SYRCLE guidelines, with narrative synthesis due to methodological heterogeneity. Ten studies met inclusion criteria, predominantly using rat or mouse contusion/compression models. NSC transplantation, often with adjuncts like hydrogels or genetic modifications (e.g., Wnt4, E-cadherin), consistently reduced proinflammatory markers (IL-1β, IL-6, and TNF-α) in 70% of studies (p < 0.05), with three demonstrating shifts toward anti-inflammatory M2 macrophages (e.g., increased CD206, arginase-1). Subacute timing enhanced efficacy, correlating with improved locomotor scores (e.g., BBB) and reduced glial scarring. However, 30% reported nonsignificant effects, attributed to chronic models or delivery methods. NSC transplantation modulates SCI inflammation by suppressing proinflammatory pathways and fostering M2 polarization, which facilitates repair. These findings point out the advantages of optimized NSC strategies for clinical translation.

Asherman Syndrome is a refractory gynecological disorder resulting from injury to the endometrium due to various causes. The treatment of choice is hysteroscopic adhesiolysis; however, recurrence rates remain high. Stem cell therapy has emerged as a promising approach for regenerating damaged endometrium in refractory cases. So, this study aims to assess the efficacy of mesenchymal stem cell therapy in refractory Asherman syndrome unresponsive to conventional treatment.