Stem Cell Reviews and Reports最新文献

Hematopoietic stem cell transplantation has been conducted in clinical settings to treat patients with malignant or non-malignant blood diseases for decades. Cord blood (CB) has been recognized as an essential graft source with beneficial characteristics, such as a lower risk of relapse and a lower rate of chronic graft-versus-host disease. However, the limited number of cells in CB impedes its broader use and hinders the ability to harness its benefits. Various expansion strategies have emerged to address this barrier, based on a deeper understanding of fate decisions and the maintenance of stemness in hematopoietic stem cells. To achieve an efficient transition from the laboratory to clinical application, several strategies have successfully managed scale-up manufacturing to satisfy clinically relevant requirements for both quality and scale. These approaches have progressed to the clinical stage and have demonstrated promising results. Novel expanded CB-derived hematopoietic stem and progenitor cells (HSPCs) therapies, including OMISIRGE (Omidubicel onlv.), Zemcelpro (Dorocubicel), and upcoming products with International Nonproprietary Name designations, introduce innovative concepts and comprehensive considerations for improving CB transplantation. This progress enables novel therapeutic options and represents a breakthrough in traditional CB transplants. In this context, we summarize and explore representative techniques and products to provide insights that inspire future developments in CB-derived HSPC therapies.

It is widely believed that epithelial cells in solid tissues undergo epithelial-mesenchymal transition (EMT) during carcinogenesis. EMT transforms polar and adherent epithelial cells in solid tumors into mesenchymal cells that get mobilized as circulating tumor cells (CTCs) and trigger metastasis. Isolating normal and neoplastic epithelial stem cells and their characterization remains challenging and vague even today. Most deaths in cancer patients are due to metastasis and hence a huge interest exists in understanding and developing tools to prevent and overcome metastasis. EMT during cancer remains clouded by controversies and questions persist as to its precise role. Besides a lack of histological evidence, lineage tracing studies have also failed to provide definitive proof supporting role of EMT in metastasis. Pluripotent, very small embryonic-like stem cells (VSELs) express sex hormone receptors and exist in a quiescent state in all tissues. They are responsible for regular turnover of epithelial cells, maintain lifelong homeostasis and their dysfunctions result in various pathologies including cancer. Developmental exposure to endocrine disrupting chemicals directly impacts VSELs, results in epigenetic changes that transform VSELs into cancer stem cells (CSCs). CSCs enter cell cycle, undergo excessive self-renewal and initiate cancer. CSCs (epigenetically altered and dysfunctional VSELs) are mobilized into circulation and are studied by our group for early prediction of cancer unlike CTCs, in a liquid biopsy, that fail to detect cancer in early stages. In this article, we discuss that besides initiation, CSCs also play a key role in cancer spread. Open questions surrounding EMT are reviewed and discussed in the context of VSELs biology. Existing hallmarks of metastasis-initiating cells produced by EMT are critically examined considering CSCs with a crucial role in cancer initiation, progression, metastasis and recurrence, challenging the existing focus on EMT and CTCs.

The concept of utilizing biological waste as a resource dates back centuries, with early practices in traditional medicine repurposing discarded tissues for healing purposes. In recent decades, advances in stem cell biology have revitalized this concept by identifying multipotent stem cells within various waste materials, including urine, adipose tissue, follicular fluid, umbilical cord blood, fetal annexes, menstrual blood, and dental pulp byproducts. These sources offer a minimally invasive, ethically sound, and cost-effective alternative to conventional stem cell harvesting methods. Stem cells derived from waste materials exhibit robust proliferative abilities and multilineage differentiation potential, positioning them as valuable tools for regenerative medicine, tissue engineering, and personalized therapeutic applications. Clinical studies highlight their promise. For example, mesenchymal stem cells from adipose tissue and umbilical cord blood have shown safety and some effectiveness in early trials. These studies report improvements of up to 30-40% in recovery scores for osteoarthritis and ischemic heart disease, as well as a 20-35% decrease in inflammatory markers for autoimmune disorders. Cord blood stem cell transplants have shown 70-90% survival rates in children with blood cancers. This underscores the clinical potential of waste-derived stem cells. However, regulatory issues limit broader use. Agencies like the U.S. Food and Drug Administration and the European Medicines Agency classify many processing methods, especially enzymatic digestion, as "more-than-minimal manipulation." This triggers strict requirements for Good Manufacturing Practice, clinical validation, and safety checks. These rules protect donors, ensure consistency, and check long-term safety. However, they also slow down clinical adoption. This review describes the history and recent advances in recycling biological waste to obtain stem cells, operating within the theoretical framework that positions waste-derived materials as viable sources for regenerative medicine. It highlights how these developments are transforming biomedical research and clinical care.

Bone regeneration is a dynamic process regulated by the interplay between the immune and skeletal systems. Regulatory T cells (Treg), a specialized subset of CD4⁺ T cells, play a crucial role in immunomodulation and bone regeneration by regulating the immune response and interacting with progenitor cells. However, the specific mechanisms through which Treg influence the osteogenic differentiation of bone marrow stromal cells (BMSC) remain unexplored. Treg were isolated from six healthy donors, expanded for 13 days, and starved for 24 h to collect Treg-conditioned media (Treg-CM). BMSC obtained from three different healthy donors were treated with Treg-CM at an optimized concentration (50 µg/mL) to assess its impact on BMSC metabolic activity, migration, and osteogenic differentiation. Label free proteomics and cytokine profiling were conducted to identify unique proteins and immunomodulatory factors in Treg-CM. The secretory cytokines of BMSC treated with Treg-CM were also analyzed. Treg-CM enhances BMSC osteogenic differentiation by upregulating the expression of key osteoblast-specific genes, increasing ALP activity, and facilitating calcium deposition. Proteomics identified unique proteins in Treg-CM that regulate cytoskeletal dynamics, metabolic processes and mRNA regulation, highlighting a complex mechanism underlying Treg-CM effects. Cytokine profiling provided key immune modulators in Treg-CM that regulate osteogenesis. Furthermore, elevated levels of MIP-1α and G-CSF were secreted by BMSC treated with Treg-CM further supporting its role in immune-mediated osteogenesis. Our findings reveal that Treg-CM enhances not only osteogenesis in vitro but also fosters a pro-regenerative microenvironment. This highlights its potential as a cell-free strategy for enhancing stem-cell based osteogenesis.

Cardiovascular disease is the leading cause of death worldwide, with myocardial infarction being the most common type among these conditions. Therefore, effective treatments for myocardial infarction are urgently needed. The regenerative capacity of cardiomyocytes (CMs) is limited, prompting an increasing number of research teams to explore cell replacement therapy as a novel approach for treating this condition. However, CMs derived from stem cells or neonatal mouse CMs often retain an immature phenotype, hindering the advancement of cell replacement therapies. Recent years have seen various methods developed for engineering cardiac tissue to enhance the maturation of induced CMs, including mechanical and biochemical stimulation, as well as co-culture techniques. Mechanical stretching, a key mechanical stimulus that simulates the physiological growth environment of the myocardium, plays a crucial role in promoting CM maturation. This review provides a comprehensive overview of the effects of mechanical stretch on CMs, discussing its mechanisms, effects, signal transduction pathways, and stimulation devices (Graphical Abstract). While mechanical stretch effectively enhances the structural and functional maturation of induced CMs, it may not be entirely sufficient on its own. Therefore, investigating combinations of multiple stimulation methods could represent a vital future research direction in cardiac tissue engineering aimed at promoting CM maturation.

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.

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.