Stem Cell Reviews and Reports最新文献

Bone organoids mimic the structure and function of actual bone tissue and serve as novel tools for disease modeling, drug testing, and bone repair. However, their development is severely impeded by the limited availability of cell sources. Fortunately, human pluripotent stem cells (hPSCs) can differentiate into organoid constituent cells, including osteoblasts, osteoclasts, and endothelial cells. However, their differentiation efficiencies are relatively low and do not meet the requirements of clinical applications because of the use of undefined culture components such as fetal bovine serum. More importantly, nearly all the existing scaffolds cannot support the culture of hPSCs. Thus, much effort should be made to construct bone organoids using cells induced from hPSCs. This review starts with the in vivo development of bone tissue. We summarize the mechanisms, methods, and purification processes for differentiating hPSCs into the above cell types in bone organoids. On this basis, we described strategies related to hPSC-based bone organoids and the growth factors and bioactive materials needed to accelerate this process. Finally, we extensively discuss the existing challenges and prospects. This review is valuable for the future development and clinical application of hPSC-derived bone organoids.

Diabetes mellitus (DM) is characterized by hyperglycemia, leading to various systemic complications. Stem cell based regenerative applications hold revolutionary potential for treating various chronic disorders, including diabetes and its associated co-morbidities. This review highlights the regenerative potential of mesenchymal stem cells (MSCs) for diabetes induced systemic manifestations i.e., damage to pancreatic beta-cells, skin, neural, retinal, and renal tissues. Persistent hyperglycemic condition in DM causes mitochondria to produce reactive oxygen species (ROS) which further activates inflammatory processes. Pro-inflammatory mediators (TNF-α, IL-1, IL-6, and C-reactive protein) lead to metabolic inflammation and damage pancreatic β-cells, blood brain barrier (BBB), synaptic integrity contributing to neurodegenerative effects, impaired glomerulus filtration rate (GFR), and blood renal barrier (BRB). MSCs evidently dictate their potential to reduce inflammation, differentiation into specific cell types, and augment tissue repair and regeneration. A number of mechanisms have been proposed by which MSCs exert their effect to improve these complications. MSCs augment β-cell function by mitigating endoplasmic reticulum stress and even translocating healthy mitochondria to injured cells. MSCs improve oxidative stress and mitochondrial dysfcunction, key processes of retinal and nerve damage. MSCs also reduce fibrosis, revive glomerular function, enhance vascular stability, promote angiogenesis and wound healing. MSC secretome, rich in bioactive metabolites, also provides retinal- and neuronal protection. MSC-based therapies have emerged as a promising hope for affected individuals. Regardless of their advantages, challenges still endure which include selection of MSC source, scalability, systemic and long-term safety, therefore, extended preclinical and clinical research is needed to standardize the treatment.

Allogeneic hematopoietic stem cell transplantation (HSCT) for pediatric acute leukemia is limited by non-relapse mortality (NRM) and relapse. This study evaluated whether the endothelial activation and stress index (EASIX) score-calculated with the formula [lactate dehydrogenase (LDH; U/L) × serum creatinine (mg/dL)]/platelets (10⁹/L)]-could be associated with NRM and overall survival (OS). We analyzed 195 patients (< 25 years) with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who underwent first-time peripheral blood HSCT at a single center between 2014 and 2022. The EASIX score was assessed pre-transplant (EASIX.PRE) and on day + 7 post-transplant (EASIX.POST). Cutoff values for EASIX.PRE (0.836) and EASIX.POST (1.632) were established using receiver operating characteristic (ROC) curves. Patients with EASIX.PRE scores below the cutoff exhibited significantly improved 12-month OS (84.67% vs. 66.12%, P = 0.028). Multivariable analysis confirmed that an EASIX.PRE score above the cutoff was an independent prognostic factor for inferior OS (HR = 1.83, P = 0.039). Similarly, patients with an EASIX.POST score below the cutoff showed a higher 12-month OS rate (87.78% vs. 72.65%, P = 0.046). However, in multivariable analysis, an EASIX.POST score above the cutoff did not demonstrate a significant relationship with reduced OS. Neither EASIX.PRE nor EASIX.POST score was independently associated with NRM, relapse, graft-versus-host disease (GvHD), leukemia-free survival (LFS), or GvHD-free, relapse-free survival (GRFS). This study highlights the prognostic utility of EASIX.PRE for OS in pediatric HSCT recipients but underscores its limited role in predicting NRM or GvHD. Further studies with larger cohorts and dynamic EASIX assessments are required to confirm these findings and refine risk stratification in pediatric HSCT.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become a valuable and widely implemented model for cardiovascular research. To obtain hPSC-CMs that resemble the native physiological or pathophysiological phenotype, numerous efforts have been made to optimize hPSC-CM differentiation protocols. The resulting methodologies posed another challenge in the field: variability in differentiation strategies. To improve reproducibility, there is a collective drive towards standardization. This review analyzed 15 years of hPSC-CMs research with a focus on oxygen handling practices during hPSC-CM differentiation. Among the 1722 research articles reviewed, six main approaches were identified whereby differentiation is performed entirely under either hypoxia or normoxia, or with switches between both conditions at specific time points. Remarkably, only 34% and 16% of the articles explicitly reported the oxygen conditions during hPSC culture and CM differentiation, respectively. This indicates that this differentiation parameter appears to be unintentionally underreported. Trend analysis of the accuracy of reporting oxygen handling over the past 15 years revealed that the proportion of articles that do not report oxygen conditions remained constant, at approximately 65% and 35% for hPSC culture and CM differentiation, respectively. On the other hand, among the articles that report conditions or cite published research, there appears to be a convergence towards a selection of the most commonly used protocols.

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in hematologic diseases by modulating immune responses, supporting hematopoiesis, and remodeling the bone marrow microenvironment. Clinically, MSCs have been explored for graft-versus-host disease and hematopoietic stem cell transplantation support, while their applications in hematologic malignancies, including acute myeloid leukemia, multiple myeloma, and myelodysplastic syndromes, remain under investigation. However, therapeutic heterogeneity, safety concerns, and standardization challenges limit their clinical translation. Recent advances in MSC-derived extracellular vesicles, gene modification technologies, and integrative combination strategies have expanded the therapeutic landscape, enabling more precise and targeted modulation of immune responses and tumor microenvironments. Moreover, disease-specific evidence highlights the dual roles of MSCs-acting either as therapeutic agents or as contributors to disease progression-depending on stromal plasticity and niche conditioning. This review provides a comprehensive and mechanistic synthesis of MSC functions across both malignant and non-malignant hematologic disorders, integrating preclinical and clinical findings in immunoregulation, hematopoietic recovery, anti-fibrosis, and microenvironmental reprogramming. In addition, we critically evaluate emerging strategies to overcome translational bottlenecks, including inter-donor variability, lack of predictive potency markers, and the need for scalable, standardized manufacturing protocols. By bridging foundational mechanisms with translational potential, this review offers forward-looking perspectives to guide future optimization and clinical integration of MSC-based therapies in hematology.

Full-thickness wound healing, particularly in chronic wounds, has remained a significant clinical challenge due to limited regenerative therapies and immune responses. Although the different biologic-based combination therapies have been suggested, the effective and safe biological adjuvants require further research and development to optimize their potential for wound healing. This study investigates the synergistic effect of menstrual blood mesenchymal stem cell-derived extracellular vesicles (MenMSC-Evs) combined with platelet-rich fibrin (PRF) on full-thickness wound healing. In this context, the MenMSC-Evs and PRF were first assessed in vitro (n = 3) for their antibacterial efficacy against E. coli, S. aureus, and P. aeruginosa. The impact of MenMSC-Evs on the proliferation and migration of HUVECs and NIH3T3 cells was evaluated to determine their influence on cellular behaviors. In vivo, a full-thickness excisional wound model was established on nine Wistar rats, with four wounds per rat assigned to different treatment groups, to evaluate wound healing. In vitro, MenMSC-Evs significantly enhanced the proliferation and migration of HUVECs by 29.3% and 11.5%, respectively, and NIH3T3 cells by 24.7% and 8.5% (p < 0.01, p < 0.001). PRF-Evs also demonstrated improved antibacterial activity, particularly against S. aureus (p < 0.001). In vivo, PRF-Evs accelerated wound closure by 23.2% (p < 0.001), increased collagen deposition (p < 0.001), and promoted angiogenesis, as evidenced by a 1.9-fold increase in VEGF-A expression and a 3.1-fold rise in CD34-positive microvessel density (p < 0.001). Moreover, PRF-Evs modulated macrophage polarization by reducing pro-inflammatory cytokines-IL-1β (8.2-fold) and TNF-α (4.4-fold)-while upregulating anti-inflammatory cytokines, including IL-10 (3.2-fold) and TGF-β (2.7-fold) (p < 0.001). In conclusion, these findings indicate that the novel combination of MenMSC-Evs and PRF offers a promising cell-free therapeutic strategy for chronic wound management by enhancing immunomodulation, promoting neovascularization, and facilitating tissue regeneration.

The integration of CRISPR-based functional genomics with pluripotent stem cell (PSC) technologies has been recognized as a transformative approach for investigating gene function, modeling human disease, and advancing regenerative medicine. The aim of this review is to provide a comprehensive evaluation of recent developments in CRISPR-Cas platforms, including gene knockouts, base and prime editing, and CRISPR activation or interference (CRISPRa/i), as applied to PSC systems. Studies employing human PSCs, including embryonic stem cells and induced pluripotent stem cells, have been examined to summarize methodologies for genome-wide screening, lineage tracing, and therapeutic engineering. Advances in editing efficiency, delivery strategies, and genomic safety have been reported, while limitations persist in the form of off-target modifications, epigenetic variability, and cell-type-specific responses. Notable applications include the generation of immune-evasive PSC lines, the development of organoid models for physiological and pathological studies, and the implementation of phenotypic screening for disease-relevant traits. Collectively, these technological and methodological advancements have established functional genomics of PSC-CRISPRSPR as a versatile and powerful framework for elucidating fundamental aspects of human biology, dissecting complex traits, and accelerating the translation of discoveries from experimental research to clinical implementation.