Stem Cell Reviews and Reports最新文献

Mesenchymal stem/stromal cells (MSCs) therapy has undoubtedly become one of the most popular treatment methods used in tissue regeneration and bioengineering in both pre-clinical and clinical trials. MSCs-based therapy has been characterized to have several benefits, mainly supporting and accelerating tissue regeneration, but at the same time it is still subjected to certain risks. The ideal MSCs population that could be used for clinical purposes should be characterized by superior homogeneity, proper safety level, and great clinical efficacy with limited or no side effects. Recently discovered, dedifferentiated fat progenitors (DFATs) could be the perfect candidates for regenerative medicine. The growing number of studies indicates DFATs superior properties compared to widely used adipose derived stem/stromal cells (ASCs). Some potentially significant differences between ASCs and DFATs have been observed in the process of isolation, their surface marker expression, proliferation ability, differentiation capacity, and expression of pluripotency-related genes. DFATs have also been shown to pose some beneficial effects in animal studies, for instance, they might contribute to bone and cartilage repair, periodontal tissue regeneration, neovascularization, skin and fat grafting, nerve tissue recovery, and intestine restoration in vivo. However, most of the published reports do not compare DFATs function directly to the well-known and used ASCs. Already found differences are inconsistent and not evaluated. Despite the growing interest in the function of DFATs in recent years, the lack of comprehensive and comparative analyses with ASCs represents a significant gap in the current literature. Therefore, it seems reasonable to organize existing data and evaluate the therapeutic potential of DFATs in comparison to the widely used ASCs. In this review, we summarized the current reports considering DFATs therapeutic properties both in vitro and in vivo. To make a clear conclusion if DFATs should be considered more beneficial, we also focused on comparing their features to the already well-investigated function of ASCs.

Background: Stroke is a leading global health concern, with cerebral infarction accounting for 62% of cases. Despite advances in acute-phase treatments, functional impairments such as motor deficits remain prevalent. This study investigates the potential of human induced pluripotent stem cell (iPSC)-derived cerebral cortical neurons for neural regeneration and motor function recovery in a female mouse model of ischemic stroke.

Methods: Cerebral infarction was induced using the Rose Bengal photothrombosis method, followed by transplantation of iPSC-derived cortical neurons into the area adjacent to the infarction. Behavioral recovery was assessed using the foot fault and cylinder tests. Histological analysis was performed to evaluate graft integration and neurite extension.

Results: Foot fault test demonstrated significant improvements in fine motor function in the transplantation group compared to the vehicle group. However, no recovery was observed in the cylinder test, which assesses gross motor function. Neurite extension from grafted cells was observed along the corticospinal tract, with axonal projections reaching the spinal cord in 68% of transplanted mice. In addition, neurite outgrowth extended to the thalamus, superior colliculus, and vestibular nucleus, suggesting integration into multiple neural circuits. Histological analysis revealed that 16.4% and 47.3% of grafted cells expressed CTIP2 and SATB2, respectively, indicating the presence of both deep- and upper-layer cortical neurons.

Conclusions: This study demonstrates that iPSC-derived cortical neurons extend axons along the corticospinal tract and can promote fine motor recovery after stroke. However, further research is needed to validate functional connectivity and long-term safety. These findings offer a promising avenue for developing cell-based therapies for stroke patients.

Background: Understanding normal development, disease modeling, and regenerative medicine forms the cornerstone of modern biomedical research. Insights into embryonic and postnatal development enable the study of cellular processes critical for tissue and organ formation.

Objectives: This review aims to summarize recent advancements in developmental biology, disease modeling techniques, and regenerative medicine, emphasizing the integration of these fields to improve therapeutic strategies.

Methods: A comprehensive literature analysis was conducted focusing on stem cell biology, tissue engineering, organoid technology, and bioengineering approaches relevant to normal development, disease modeling, and regenerative therapies.

Results: Advances in stem cell technologies, including embryonic and induced pluripotent stem cells, have facilitated transplantation therapies and tissue regeneration. The emergence of 3D multicellular culture systems, such as organoids, enhances disease modeling by more accurately replicating tissue architecture. Bioengineered organ germs represent a promising strategy for functional organ regeneration. However, challenges remain in mimicking the complex in vivo environment and addressing ethical and technical limitations.

Conclusions: Multicellular and three-dimensional in vitro models represent critical tools for bridging gaps in our understanding of development, disease, and regeneration. Continued interdisciplinary efforts are essential to translate these findings into effective regenerative therapies and precise disease models.

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.