Stem Cell Reviews and Reports最新文献

Hematopoiesis is a dynamic, adaptive process that governs blood and immune cell production through coordinated self-renewal, proliferation and differentiation. Shaped by intrinsic cell heterogeneity, environmental cues and physiological demands, it ensures effective blood cell production under both steady-state and stress conditions. Advances in single-cell and lineage-tracing technologies have shifted the traditional hierarchical view of hematopoiesis toward a flexible, interconnected network. B cell development exemplifies this plasticity, involving coordinated genetic and environmental signals to generate diverse subsets. Beyond the classical common lymphoid progenitors (CLP)-dependent model, B cells can also arise through alternative pathways, including direct differentiation from HSCs or at extramedullary sites like the spleen. Environmental signals and niche-specific factors support this diversity. Bipotent progenitors linking B lymphoid and myeloid (macrophage/osteoclast) fates have been identified in both fetal and adult hematopoiesis, revealing overlapping lineage potential and developmental flexibility. Moreover, mature B cells exhibit functional adaptability. B2 cells can convert into B1 cells under certain conditions, while CD11b⁺ myeloid-like B cells (M-B cells) emerge during emergency myelopoiesis, highlighting functional plasticity beyond antibody production. This evolving understanding redefines B cells as versatile immunoregulatory players, especially during inflammation and immune stress and opens new avenues for therapeutic interventions in immunity and hematologic disorders.

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.

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.