Search Results (45)

Background: Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is often attributed to immaturity, although this has never been conclusively demonstrated. The emergence of stem cells and their effective medical applications has intensified research into spinal cord regeneration. However, despite these advances, the impact of clinical trials involving spinal cord-injured (SCI) patients remains disappointingly low. Long-distance regeneration has yet to be proven. Methods: Our study involved a microsurgical dorsal myelotomy in fetal rats. The development of pioneering long primary afferent axons during early gestation was examined long after birth. Results: A single cut triggered the intrinsic ability of the dorsal root ganglion (DRG) neurons to reprogram. Susceptibility to hypoxia caused the axons to stop developing. However, the residual axonal outgrowth sheds light on the intriguing temporal and spatial events that reveal long-distance CNS regeneration. The altered phenotypes displayed axons of varying lengths and different features, which remained visible throughout life. The previously designed developmental blueprint was crucial for interpreting these enigmatic features. Conclusions: This research into immaturity enabled the exploration of the previously impenetrable domain of early life and the identification of a potential missing link in CNS regeneration research. Central axon regeneration appeared to occur much faster than is generally believed. The paradigm provides a challenging approach for exhaustive intrauterine reprogramming. When the results demonstrate pre-clinical effectiveness in CNS regeneration research, the transformational impact may ultimately lead to improved outcomes for patients with spinal cord injuries. Full article

Background: The process of prenatal hematopoiesis occurs in various anatomical locations, including the placenta. The placenta is not merely a temporary hematopoietic reservoir, but it is one of the key sites for the synthesis of hematopoietic stem cells (HSCs). This study aimed to investigate the presence, distribution, and immunoprofiles of HSCs in the human placenta during different gestational periods. Materials and Methods: Placental samples of different gestational ages (first, second, and third trimesters) were analyzed using classical hematoxylin and eosin staining and immunohistochemical staining for CD34, CD117, and CD41 markers, with HSC quantification through numerical areal density (N_A). Results: Highly immunoreactive CD34 HSCs were present in placentas throughout gestation, while highly immunoreactive CD117 and CD41 HSCs were observed during the first two trimesters. In the first trimester, HSCs were found within the lumen of blood vessels and as individual cells in the mesenchyme of chorionic villi. With advancing gestation, the number of HSCs in the mesenchyme of chorionic villi increased. Conclusions: Immunoreactive CD34, CD117, and CD41 cells are present in significant proportions in various parts of the placenta throughout gestation, indicating that the placenta provides a substantial proportion of HSCs for hematopoiesis. Full article

Background: Thrombospondin-1 (TSP-1) is an extracellular glycoprotein that mediates the differentiation of pulmonary endothelial cells and specialized stem cells into alveolar epithelial lineage-specific cells during the repair phase after lung injury. Since bronchopulmonary dysplasia (BPD) involves the inhibition of lung development with altered lung structure and vasculature, differential expression of the THBS-1 gene may impact lung development and pulmonary endothelial cell repair and have an important role in BPD. Methods: This prospective single-center cohort study included ELBW infants with and without BPD. DNA from buccal swabs underwent RT-PCR with TaqMan probes, and TSP-1 protein was measured in tracheal aspirates. Statistical analyses used Chi-square tests, Fisher’s exact tests, Wilcoxon Rank Sum tests, and t-tests (p < 0.05). Results: ELBW infants with BPD had significantly lower gestational ages and birth weights compared to those without BPD [25 (24,26) and 27 (25,28) weeks; median (IQR); p = 0.008] and [712 (155) and 820 (153) grams; mean (SD); p = 0.002], respectively. There were significant differences in the haplotype distributions of THBS1 variants rs2664139/rs1478604 (p = 0.006) and THBS1 variants rs1478605/rs1478604 (p = 0.008) between no-BPD and BPD groups. There were also significant differences in airway TSP-1 protein levels between moderate and severe BPD patients [(p = 0.02) (no BPD: 527 (114–1755); moderate BPD: 312 (262–641); and severe BPD 211: (117–352) ng/dL; median (IQR)]. Conclusions: Although no individual variants differed, two THBS1 haplotypes and early TSP-1 airway expression varied by BPD severity, suggesting a role for TSP-1 in lung development and BPD pathogenesis in ELBW infants. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses before 24 weeks of gestation. It affects 3–5% of women who are attempting to conceive. RPL can stem from a variety of causes and is frequently associated with psychological distress and a diminished quality of life. By contrast, recurrent implantation failure (RIF) refers to the inability to achieve a successful pregnancy after three or more high-quality embryo transfers or at least two instances of egg donation. RIF shares several causative factors with RPL. The immunological underpinnings of these conditions involve alterations in uterine NK cells, reductions in M2 macrophages and myeloid-derived suppressor cells, an increased Th1/Th2 ratio, a decreased Treg/Th17 ratio, the presence of shared ≥3 HLA alleles between partners, and autoimmune disorders. Various therapeutic approaches have been employed to address these immunological concerns, achieving varying degrees of success, although some therapies remain contentious within the medical community. This review intends to explore the immunological factors implicated in RPL and RIF and to analyze the immunological treatments employed for these conditions, which may include steroids, intravenous immunoglobulins, calcineurin inhibitors, anti-TNF antibodies, intralipid infusions, granulocyte colony-stimulating factor, and lymphocyte immunotherapy. Full article

To investigate prenatal muscle satellite cell (MuSC) development and the associated epigenetic modifications in yak. Here, we conducted morphological and protein co-localization analyses of fetal longissimus dorsi muscle at various developmental stages using histology and immunofluorescence staining methods. Our study observed that primary muscle fibers began forming at 40 days of gestation, fully developed by 11 weeks, and secondary muscle fibers were predominantly formed by around 105 days. Throughout development, MuSCs were mainly located between the muscle fiber membrane and the basement membrane, acting as a reserve for the stem cell pool. MuSCs appeared within myotubes only during critical phases of primary and secondary muscle fiber formation. The proliferation of MuSCs gradually decreases until birth. MuSCs with 5mC modification show a trend of increasing first and then decreasing. MuSCs with 5hmC modification also present a dynamic change trend. The 41st day and 11th week are the critical periods for the changes of both. From the 11th week to around the 110th day of gestation, the modification effect of histone H3K4me3 is crucial for MuSCs during the development of the fetal longissimus dorsi muscle. Combined, our data identify key time points for yak fetal skeletal muscle growth and development and demonstrate that DNA methylation and histone modifications in MuSCs are closely related to this process, offering a valuable basis for future research into the molecular mechanisms underlying yak muscle development. Full article

Chronic kidney disease (CKD) affects more than 10% of the world’s population. Hemodialysis, along with peritoneal dialysis and renal transplant, is one of the renal replacement therapies offered to patients with CKD/end-stage renal disease (ESRD). To proceed with hemodialysis, vascular access is required. The two means of long-term access are arteriovenous fistula (AVF) and arteriovenous graft (AVG). Multiple therapies have been created to help the long-term patency of AVFs. These therapies are needed as 40% of AVFs fail within the first year and additional intervention is required. Much of the existing research has focused on biomarkers, immune cells, hypoxia, and cell-based therapies. Regeneration therapy using mesenchymal stem cells seeks to investigate other ways that we can treat AVF failure. Mesenchymal stem cells are harvested as two main types, fetal and adult. Fetal cells are harvested at different times in fetal gestation and from multiple sources, placental blood, Whartons jelly, and amniotic stem cell fluid. Taken together, this review summarizes the different preclinical/clinical studies conducted using different types of MSCs towards vascular regenerative medicine and further highlights its potential to be a suitable alternative approach to enhance AVF patency. Full article

Biological aging is defined as a progressive decline in tissue function that eventually results in cell death. Accelerated biologic aging results when the telomere length is shortened prematurely secondary to damage from biological or environmental stressors, leading to a defective reparative mechanism. Stem cells therapy may have a potential role in influencing (counteract/ameliorate) biological aging and maintaining the function of the organism. Mesenchymal stem cells, also called mesenchymal stromal cells (MSCs) are multipotent stem cells of mesodermal origin that can differentiate into other types of cells, such as adipocytes, chondrocytes, and osteocytes. MSCs influence resident cells through the secretion of paracrine bioactive components such as cytokines and extracellular vesicles (EVs). This review examines the changes in telomere length, cellular senescence, and normal biological age, as well as the factors contributing to telomere shortening and accelerated biological aging. The role of MSCs—especially those derived from gestational tissues—in prevention of telomere shortening (TS) and accelerated biological aging is explored. In addition, the strategies to prevent MSC senescence and improve the antiaging therapeutic application of MSCs and MSC-derived EVs in influencing telomere length and cellular senescence are reviewed. Full article

A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alterations in placenta-specific androgen signalling, a signalling axis that involves the androgen receptor (AR)-mediated regulation of target genes containing androgen response elements (AREs). In this study, we examined global and ARE-specific transcriptomic signatures in term male placentae (≥37 weeks of gestation) across BWC subcategories (<10th, 10th–30th, >30th) using RNA-seq and gene set enrichment analysis. ARE-containing transcripts in placentae with BWCs below the 10th percentile were upregulated compared to those in the 10th–30th and >30th percentiles, which coincided with the enrichment of gene sets related to hypoxia and the suppression of gene sets associated with mitochondrial function. In the absence of ARE-containing transcripts in silico, <10th and 10th–30th BWC subcategory placentae upregulated gene sets involved in vasculature development, immune function, and cell adhesion when compared to those in the >30th BWC subcategory. Collectively, our in silico findings suggest that changes in the expression of ARE-containing transcripts in male placentae may contribute to impaired placental vasculature and therefore result in reduced fetal growth outcomes. Full article

An adverse perinatal environment can increase long-term cancer risk, although the precise nature of associated perinatal triggers remain unknown. Sleep apnea is a common condition during pregnancy, characterized by recurrent cessations in breathing during sleep, and the potential consequences of sleep apnea during pregnancy as it relates to breast cancer risk in offspring have not been explored. To model sleep apnea, Sprague-Dawley dams were exposed during gestation to nightly intermittent hypoxia (GIH) or normoxia (GNx), and the mammary glands of female offspring were examined. GIH offspring demonstrated increased epithelial stem and progenitor cell populations, which are associated with diminished transforming growth factor beta (TGFβ) activity. Elevations in adipose tissue stem cells in the mammary gland were also identified in GIH offspring. In aging females, mammary tumors formed in GIH offspring. These tumors displayed a dramatic increase in stroma compared to tumors from GNx offspring, as well as distinct patterns of expression of stem cell-related pathways. Together, these results suggest that exposure to sleep apnea during pregnancy leads to lasting changes in the mammary glands of female offspring. Increased stem and progenitor cell populations as a result of GIH exposure could enhance long-term breast cancer risk, as well as alter the clinical behavior of resulting breast tumors. Full article

Over the past 20 years, stem cell therapy has been considered a promising option for treating numerous disorders, in particular, neurodegenerative disorders. Stem cells exert neuroprotective and neurodegenerative benefits through different mechanisms, such as the secretion of neurotrophic factors, cell replacement, the activation of endogenous stem cells, and decreased neuroinflammation. Several sources of stem cells have been proposed for transplantation and the restoration of damaged tissue. Over recent decades, intensive research has focused on gestational stem cells considered a novel resource for cell transplantation therapy. The present review provides an update on the recent preclinical/clinical applications of gestational stem cells for the treatment of protein-misfolding diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). However, further studies should be encouraged to translate this promising therapeutic approach into the clinical setting. Full article

Congenital tumors are rare and, owing to this rarity, there is limited information on many of them. A total of 839 fetal and postnatal MRI studies performed in the first 3 months of life were retrospectively reviewed. They were performed with the use of 1.5 T scanners. Seventy-six tumors were diagnosed based on fetal MRI between 20 and 37 gestational weeks, and 27 were found after birth, from 1 day of age to 3 months of life. Teratomas were the most common tumors in our dataset, mainly in the sacrococcygeal region (SCT), followed by cardiac rhabdomyomas and subependymal giant cell astrocytomas (SEGA) associated with TSC, and neuroblastomas. The group of less common tumors consisted of infantile fibrosarcomas, malignant rhabdoid tumors, mesoblastic nephromas and Wilms tumor, craniopharyngiomas, brain stem gliomas, desmoplastic infantile astrocytoma, choroid plexus carcinoma, glioblastoma, hemangiopericytoma, rhabdomyosarcoma, melanoma, mesenchymal hamartomas of the chest wall and the liver, and juvenile xanthogranuloma, with special consideration of blue rubber bleb nevus syndrome. MRI plays a significant role in further and better characterization of congenital tumors, leading to a correct diagnosis in many cases, which is crucial for pregnancy and neonatal management and psychological preparation of the parents. No diagnosis is impossible and can be absolutely excluded. Full article

Maternal folic acid intake has important effects on offspring growth and development. The mechanism involved in the renewal of intestinal epithelial cells remains unclear. Thus, this study aimed to investigate the potential effect of maternal folic acid supplementation during gestation and lactation on the structural and functional development of the small intestine in piglet offspring. Twenty-four Duroc sows were assigned to a control group (CON) and a folic-acid-supplemented group (CON + FA, supplemented with 15 mg/kg of folic acid). The results showed that maternal folic acid supplementation throughout gestation and lactation significantly increased the body weight, serum folate level, and intestinal folate metabolism in piglets. It also improved the villus length, villus height-to-crypt depth ratio, and transcript levels of nutrient transporters (GLUT4, SNAT2, FABP2, and SLC7A5) in piglets’ duodenum and jejunum. In addition, maternal folic acid supplementation increased Ki67-positive cells and the expression of proliferation-related marker genes (C-Myc, CyclinD1, and PCNA) in piglets’ intestinal stem cells. It also boosted the expression of genes associated with mature secreted cells (ChrA, Muc2, Lyz, Vil1), indicating enhanced proliferation and differentiation of intestinal stem cells. These findings demonstrate that maternal folic acid supplementation enhances growth performance and gut health in piglet offspring by promoting epithelial cell renewal equilibrium. Full article

Scar formation during normal tissue regeneration in adults may result in noticeable cosmetic and functional defects and have a significant impact on the quality of life. In contrast, fetal tissues in the mid-gestation period are known to be capable of complete regeneration with the restitution of the initial architecture, organization, and functional activity. Successful treatments that are targeted to minimize scarring can be realized by understanding the cellular and molecular mechanisms of fetal wound regeneration. However, such experiments are limited by the inaccessibility of fetal material for comparable studies. For this reason, the molecular mechanisms of fetal regeneration remain unknown. Mesenchymal stromal cells (MSCs) are central to tissue repair because the molecules they secrete are involved in the regulation of inflammation, angiogenesis, and remodeling of the extracellular matrix. The mesodermal differentiation of human pluripotent stem cells (hPSCs) recapitulates the sequential steps of embryogenesis in vitro and provides the opportunity to generate the isogenic cell models of MSCs corresponding to different stages of human development. Further investigation of the functional activity of cells from stromal differon in a pro-inflammatory microenvironment will procure the molecular tools to better understand the fundamental mechanisms of fetal tissue regeneration. Herein, we review recent advances in the generation of clonal precursors of primitive mesoderm cells and MSCs from hPSCs and discuss critical factors that determine the functional activity of MSCs-like cells in a pro-inflammatory microenvironment in order to identify therapeutic targets for minimizing scarring. Full article

Today, it is recognized that medicines will eventually be needed during pregnancy to help prevent to, ameliorate or treat an illness, either due to gestation-related medical conditions or pre-existing diseases. Adding to that, the rate of drug prescription to pregnant women has increased over the past few years, in accordance with the increasing trend to postpone childbirth to a later age. However, in spite of these trends, information regarding teratogenic risk in humans is often missing for most of the purchased drugs. So far, animal models have been the gold standard to obtain teratogenic data, but inter-species differences have limited the suitability of those models to predict human-specific outcomes, contributing to misidentified human teratogenicity. Therefore, the development of physiologically relevant in vitro humanized models can be the key to surpassing this limitation. In this context, this review describes the pathway towards the introduction of human pluripotent stem cell-derived models in developmental toxicity studies. Moreover, as an illustration of their relevance, a particular emphasis will be placed on those models that recapitulate two very important early developmental stages, namely gastrulation and cardiac specification. Full article

Induced pluripotent stem cells (iPSCs) can differentiate into all types of cells and can be used in livestock for research on biological development, genetic breeding, and in vitro genetic resource conservation. The Bactrian camel is a large domestic animal that inhabits extreme environments and holds value in the treatment of various diseases and the development of the local economy. Therefore, we transferred four mouse genes (Oct4, Sox2, Klf4, and c-Myc) into Bactrian camel fetal fibroblasts (BCFFs) using retroviruses with a large host range to obtain Bactrian camel induced pluripotent stem cells (bciPSCs). They were comprehensively identified based on cell morphology, pluripotency gene and marker expression, chromosome number, transcriptome sequencing, and differentiation potential. The results showed the pluripotency of bciPSCs. However, unlike stem cells of other species, late formation of stem cell clones was observed; moreover, the immunofluorescence of SSEA1, SSEA3, and SSEA4 were positive, and teratoma formation took four months. These findings may be related to the extremely long gestation period and species specificity of Bactrian camels. By mining RNA sequence data, 85 potential unique pluripotent genes of Bactrian camels were predicted, which could be used as candidate genes for the production of bciPSC in the future. Among them, ASF1B, DTL, CDCA5, PROM1, CYTL1, NUP210, Epha3, and SYT13 are more attractive. In conclusion, we generated bciPSCs for the first time and obtained their transcriptome information, expanding the iPSC genetic information database and exploring the applicability of iPSCs in livestock. Our results can provide an experimental basis for Bactrian camel ESC establishment, developmental research, and genetic resource conservation. Full article