Stem Cell Reviews and Reports最新文献

Preterm infants face a heightened risk of various complications due to the immaturity of their physiological systems, with global rates of preterm birth increasing. These complications represent the leading causes of mortality in children. This review examines current research on the use of umbilical cord blood(UCB) for managing preterm complications, including bronchopulmonary dysplasia(BPD), hypoxic ischemic encephalopathy(HIE), necrotizing enterocolitis(NEC), sepsis and retinopathy of prematurity(ROP). UCB is rich in bioactive components, including hematopoietic stem cells(HSCs), mesenchymal stem cells(MSCs), and exosomes, which are crucial for neurological and vascular repair, anti-apoptosis, anti-inflammation, and immunomodulation. Both preclinical investigations and clinical trials have highlighted the potential of UCB therapy in mitigating the severity of preterm complications, enhancing clinical outcomes, and fostering long-term neural development. Current clinical studies aim to further confirm the safety and efficacy of UCB therapy, with future research concentrating on refining treatment protocols and tailoring personalized medical approaches to enhance the long-term well-being of preterm infants.

The presence of neural stem cells (NSCs) of the subventricular and subgranular zone in the adult mammalian brain has been the focus of much attention; however, these high-function centers have low regenerative ability in response to brain damage. In this review, we focus on the mediobasal hypothalamus (MBH)-a diencephalic region lining the floor of the third ventricle-and the medulla oblongata, a brainstem structure. Both contain niche-like glial populations with context-dependent neurogenic and gliogenic potential. These evolutionarily conserved regions contain neural circuits essential for life support and display high regenerative capacity in lower vertebrates. Recently, NSCs and neural progenitor cells (NPCs) have been reported in the MBH, including the arcuate nucleus and median eminence. Mediobasal hypothalamic tanycytes, with proximal cell bodies facing the third ventricle and distal cellular processes toward the parenchyma, are identified as NSCs that supply various progenitor and ependymal cells. Neural circuits of the MBH exhibit relatively regenerative capability with near-complete or alternative neuronal circuit reorganization after hypothalamic neuronal damage. In the medulla oblongata, there are two types of NSCs: astrocyte-like NSCs in the area postrema and tanycyte-like NSCs in the central canal facing the cerebrospinal fluid. Astrocyte-like NSCs exhibit relatively active proliferation, whereas tanycyte-like NSCs are almost quiescent. Monosodium glutamate selectively induces neuronal cell death in the area postrema, and NPCs proliferate and differentiate into mature neurons, resulting in near-complete restoration of neuronal density. Experimental autoimmune encephalomyelitis causes demyelination in the medulla oblongata, and NSCs partially restore the density of oligodendrocytes. Thus, recent studies indicate that the adult MBH and medulla oblongata exhibit context-dependent regenerative responses, supplying new neurons and oligodendrocytes in response to brain damage.

Small extracellular vesicles derived from umbilical cord mesenchymal stem cells (UC-sEvs) may be used for the treatment of idiopathic pulmonary fibrosis (IPF) because of their ability to control inflammation and inhibit fibrosis. However, the lack of clarity regarding the treatment mechanism of IPF and the corresponding quality standards limit the clinical application of these small extracellular vesicles. Here, we established a good manufacturing practice (GMP) grade process for isolating UC-sEvs, and RNA-seq was performed to screen for potential therapeutic cargo in the product to confirm the therapeutic effect of nebulized UC-sEv agents against IPF. Functionally, UC-sEvs inhibited the pulmonary inflammatory response by regulating macrophage function, thereby suppressing the bleomycin toxicity-induced progression of fibrosis. Mechanistically, miR-146a-5p enrichment in UC-sEvs may be involved in alleviating bleomycin-induced IPF by targeting TRAF6/IRAK1 to negatively regulate inflammation. The proposed quality control strategy ensures the stability of the product across three batches, with RNA-seq analysis revealing highly similar miRNA expression profiles. The feasibility of using miR-146a-5p as a key therapeutic molecule has been validated. Finally, on the basis of the results of pharmacodynamics and key therapeutic molecule studies, we provided a detailed quality control standard for IPF therapy by nebulizing UC-sEv. These findings help understand how sEvs impact IPF and the possible consequences of their therapeutic usage and offer a quality standard reference.

Capillary malformation (CM) is a congenital vascular anomaly that affects the skin, mucosa, eye, and brain. A major obstacle to mechanistic and drug screening studies for CM has been the lack of preclinical models. In this study, we established vascular organoids (VOs) generated through the self-assembly of vascular lineages of endothelial cells and smooth muscle cells differentiated from CM-induced pluripotent stem cells (iPSC). Within these VOs induced endothelial cells and smooth muscle cells organized into juxtapositions to form vascular branches. CM patient iPSC-derived VOs showed a higher density of endothelial and smooth muscle cell populations and greater vascular branch lengths as compared with VOs derived from iPSCs generated from healthy skin biopsies. Overall, this study represents the first disease-relevant VO model of CM, providing a valuable platform for future mechanistic studies and drug screening.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease in which the contribution of vascular alterations remains poorly understood. While most previous studies focused on epithelial and fibroblast dysfunction, recent evidence suggests that endothelial cell injury and vascular remodeling are integral to disease pathogenesis. This study aimed to longitudinally characterize the circulating endothelial compartment in IPF and explore its association with clinical outcomes. In this multicenter substudy of the COFI (COhorte FIbrose) prospective cohort, 95 patients with IPF underwent 243 serial assessments of circulating endothelial biomarkers. These included the quantification of circulating endothelial cells (CECs) using immunomagnetic isolation, and CD34⁺CD45^DIM cells, total CD34⁺ cells, and the proportions of CD34⁺KDR⁺ and CD34⁺CD133⁺ subsets within the CD34⁺ population, assessed by flow cytometry. In addition, hematopoietic endothelial progenitor cells (hEPCs) and endothelial colony-forming cells (ECFCs) were measured using standardized culture-based assays. Longitudinal analysis revealed a significant increase in CD34⁺KDR⁺ progenitor cells (p = 0.04) and CECs (p = 0.03) over time. ECFCs showed no significant variation. Higher BMI was associated with lower levels of CD34⁺KDR⁺ cells (p = 0.04), CD34⁺CD133⁺ cells (p = 0.05), whereas ECFCs were undetectable in obese patients (median 0 [0-0], p = 0.063). Multivariate analysis indicated no significant associations between baseline levels of any endothelial biomarkers and progression-free survival, exacerbation, or mortality. To the best of our knowledge, this study provides the first multicenter longitudinal profiling of the circulating endothelial compartment in IPF. Our findings suggest that endothelial dysfunction reflects a chronic, possibly secondary process in IPF rather than a primary driver of fibrosis. Circulating endothelial biomarkers may offer insight into disease activity and therapeutic response.

Rationale: Although direct cardiac delivery of bone marrow-derived mesenchymal stromal cells (MSCs), c-kit-positive (c-kit^POS) cardiac progenitor cells (CPCs), and cardiac mesenchymal cells (CMCs) is beneficial in preclinical models of chronic ischemic cardiomyopathy (ICM), the optimal route of cell administration and the comparative efficacy of these cell types remain unclear. Addressing these issues is important to inform translational studies of heart failure (HF).

Objective: To directly compare the effects of 3 repeated intravenous infusions of syngeneic MSCs, CPCs, and CMCs in a well-established rat model of chronic ICM.

Methods and results: Rats with a 30-day-old myocardial infarction (MI) received 3 repeated intravenous infusions, 35 days apart, of vehicle (Dulbecco's phosphate-buffered saline [DPBS]), MSCs, CMCs, or CPCs, at a dose of 12 × 10⁶ cells. The left ventricular (LV) function was assessed by serial echocardiography and by hemodynamic studies at the end of the protocol. Results showed that all three types of cells improved LV function assessed by echocardiography, but only MSCs and CPCs improved hemodynamic indices of LV function. In the noninfarcted LV region, all three cell types reduced fibrosis, but only MSCs and CPCs reduced cardiomyocyte cross-sectional area and CD45 positive cell infiltration.

Conclusions: Three repeated intravenous infusions of allogeneic MSCs, CPCs, or CMCs improved echocardiographic measures of LV function and reduced myocardial fibrosis in rats with chronic MI. However, only MSCs and CPCs improved hemodynamic indices of LV function and reduced hypertrophy and inflammation in the viable, noninfarcted myocardium. These data confirm the effectiveness of intravenous cell delivery in alleviating ICM and suggest therapeutic superiority of MSCs and CPCs over CMCs.

Congenital heart defects (CHDs), ranging from minor issues to critical malformations requiring urgent and ongoing medical care, are structural heart abnormalities present at birth. Historically, the prognosis for CHD patients was poor; however, advancements in medical treatments have significantly improved survival rates, with approximately 90% of children with CHDs now reaching adulthood. Standard CHD treatments include cardiac catheterization, heart surgery, medications, and, in severe cases, heart transplantation. Despite these advancements, innovative approaches are urgently needed to enhance therapeutic outcomes and overcome the limitations of current treatments. Recently, the integration of stem cell technologies with bio-scaffold engineering has garnered substantial attention. Key breakthroughs include the development of resilient biological scaffolds designed to expand and remodel within the heart, potentially overcoming the limitations of existing prostheses. Promising regenerative CHD treatments emerge from decellularized extracellular matrix scaffolds combined with autologous stem cells. Tissue engineering and pre-vascularization technologies aim to create functional heart tissues capable of growing with the child, thus reducing the need for multiple procedures. Enhanced scaffold fabrication techniques, such as 3D bioprinting, nanofiber scaffolds, and biomimetic fixation methods, have significantly advanced the field. These technologies enable better integration with native cardiac tissues and allow precise control over scaffold properties. Additionally, innovations in hybrid and smart scaffolds, along with bioreactor conditioning, further amplify the regenerative potential of engineered cardiac tissues. This review focuses on the convergence of stem cell therapy and bio-scaffold technology, highlighting the latest advancements in CHD treatment. It explores the evolution of novel materials and methodologies aimed at creating flexible, durable solutions for managing CHDs. By combining regenerative medicine with cutting-edge scaffold engineering, these emerging therapies offer hope for improved outcomes and quality of life for individuals affected by CHDs.

Cardiovascular disease (CVD) is a significant cause of cardiac and vascular-related deaths worldwide. While traditional drug and surgical treatments can alleviate symptoms and slow progression, they cannot regenerate heart tissue or reverse function. Heart transplantation, although a radical cure, is limited by donor availability, risks, and costs. Stem cell therapy has gained attention as a potential treatment option, but is hindered by low retention rates post-transplantation. Extracellular vesicles (EVs) are nanoscale membrane vesicles found in various cells and play a key role in the paracrine effects of stem cells. Despite being a promising treatment for cardiovascular diseases, the short plasma half-life and non-specific uptake by the liver and spleen significantly impact its therapeutic efficacy in the heart. This review examines the current understanding of extracellular vesicles and recent advancements in strategies to reduce EV loss and enhance targeted delivery for cardiovascular disease treatment. Approaches such as hydrogel incorporation, vesicular membrane modifications, fusion techniques, and inhibition of monocyte-macrophage system (MPS) clearance are discussed. The paper concludes by addressing the current status of extracellular vesicle therapy and provides insights into its future development.