Iron stores at birth in a full-term normal birth weight birth cohort with a low level of inflammation

Iron stores at birth are essential to meet iron needs during the first 4–6 months of life. The present study aimed to investigate iron stores in normal birth weight, healthy, term neonates. Umbilical cord blood samples were collected from apparently normal singleton vaginal deliveries (n=854). Subjects were screened and excluded if C-reactive protein (CRP) > 5 mg/l or α1-acid glycoprotein (AGP) > 1 g/l, preterm (<37 complete weeks), term < 2500g or term > 4000g. In total, 762 samples were included in the study. Serum ferritin, soluble transferrin receptor (sTfR), hepcidin, and erythropoietin (EPO) were measured in umbilical cord blood samples; total body iron (TBI) (mg/kg) was calculated using sTfR and ferritin concentrations. A total of 19.8% newborns were iron deficient (ferritin 35 μg/l) and an additional 46.6% had insufficient iron stores (ferritin < 76 μg/l). There was a positive association between serum ferritin and sTfR, hepcidin, and EPO. Gestational age was positively associated with ferritin, sTfR, EPO, and hepcidin. In conclusion, we demonstrate a high prevalence of insufficient iron stores in a Chinese birth cohort. The value of cord sTfR and TBI in the assessment of iron status in the newborn is questionable, and reference ranges need to be established.     

Clinical analysis of human umbilical cord mesenchymal stem cell allotransplantation in patients with premature ovarian insufficiency

ObjectivePremature ovarian insufficiency (POI) is a refractory disease that seriously affects female fertility. Growing body of evidence has indicated mesenchymal stem cells (MSCs) as promising resources in regenerative medicine. In this study, we treated POI patients with umbilical cord‐derived MSCs (UCMSCs) and then investigated the restoration of ovarian function and clinical outcomes through follow‐ups.Materials and methodsSixty‐one patients diagnosed with POI participated in this study. UCMSCs were isolated and cultured according to GMP standards, and then transplanted to the patients’ ovary by orthotopic injection under the guidance of vaginal ultrasound. We monitored side effects, vital signs and changes in clinical and collected haematological and imaging parameters during the follow‐ups.ResultsAll patients showed normal clinical behaviour without serious side effects or complications relevant to the treatment. Transplantation of UCMSCs rescued the ovarian function of POI patients, as indicated by increased follicular development and improved egg collection. POI patients who experienced shorter amenorrhoea durations (<1 year) seemed to obtain mature follicles more easily after stem cell therapy, and patients with better ovarian conditions (pre‐operative antral follicles) were more likely to derive the better outcomes by UCMSC injection. Four successful clinical deliveries were obtained from POI patients after UCMSC transplantation, and all of these babies are developed normally.ConclusionsThe clinical trial result sugggests a possible therapy for POI by UCMSC transplantation.     

Human umbilical cord tissue stem cells and neuronal lineages in an injectable caffeic acid–bioconjugated gelatin hydrogel for transplantation

Present-day scaffolds are useful in cell therapy to a reasonable extent, but in pursuit of improvising the scaffold to improve the outcome, we tested a new injectable caffeic acid–bioconjugated gelatin hydrogel scaffold (CBGH; with tunable stiffness −10%). Two-dimensional (2D) form of human umbilical cord tissue-derived mesenchymal stem cells (HUCMSCs) culture performed based on our previously reported methods and characterized by using multipotent and pluripotent analysis. In addition, neurogenesis was induced in the presence of retinoic acid or neural growth factor or epidermal growth factor categorized by neuronal markers. The viability, proliferation rate, and vascular endothelial growth factor expression of HUCMSCs increased significantly in the CBGH scaffold. In addition, there was an increase in CD90 and TRA-1-81 phenotypic expressions and SOX-2, MAP-2, TAU, NeuN, and NF, which confirmed the neurogenesis of encapsulated HUCMSCs. Topographical elucidation by scanning electron microscopy data showed that the HUCMSCs proliferated and migrated inside the construct. Hematoxylin and eosin staining demonstrated a more viable structural pattern and cresyl violet staining showed the Nissl synthesis, confirming the presence of functional neurons in the encapsulated form. The molecular-level analysis further substantiated that HUCMSCs cultured in CBGH expressed significantly greater upregulation of stemness, neuronal genes, and protein expression compared with the adherent culture. Correspondingly, this is the first time that we have measured the fluorescence intensity variation of the HUCMSCs-stained cell segmentation process using customized MATLAB code execution to reduce the background noise and autofluorescence. We conclude that this novel CBGH scaffold increases the viability, proliferation, stemness, and also neuronal transdifferentiation of HUCMSCs in a three-dimensional culture than the 2D plastic adherent culture.     

Triad1 regulates the expression and distribution of EHD1 contributing to the neurite outgrowth of neurons after spinal cord injury

Traumatic spinal cord injury is a common and severe complication after an accident. As we all know that neurite outgrowth of neurons is difficult after a spinal cord injury. Endosome system is associated with cargoes transportation and contributes in promoting the neuronal capability for neurite outgrowth. EH domain-containing protein 1 (EHD1) transports proteins through the endosome system, especially in the recycling endosomes and regulating the neurite outgrowth. In mammalian cells, the involvement of the ubiquitin-proteasome system in endosomal sorting has been well established. Two RING fingers and a DRIL (double RING finger-linked) 1 (Triad1) plays an important role in membrane trafficking and its mutant results in the wrong accumulation of receptors in endosomes and plasma membrane. In this current study, we reasonably integrated the results of the above research and investigated the regulating function of Triad1 to EHD1 following the spinal cord injury. We characterized the upregulated expression and distribution of Triad1 and EHD1 in the neurons after SCI and declared the interaction between Triad1 with EHD1 both in vitro and in vivo. Triad1 regulated the interaction between itself and the full-length or EH domain of EHD1, which influenced the neurite outgrowth of PC12 cells. Our data delineate a novel interaction between Triad1 and EHD1 that may contribute to the regulation of neurite outgrowth for neurons after the spinal cord injury.     

Neuromodulatory Selection of Motor Neuron Recruitment Patterns in a Visuomotor Behavior Increases Speed

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Condensation of the Drosophila nerve cord is oscillatory and depends on coordinated mechanical interactions

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WJSC 6th Anniversary Special Issues（1）:Hematopoietic stem cell transplantation Allogeneic hematopoietic cell transplant for acute myeloid leukemia:Current state in 2013 and future directions

Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free survival.Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk.Allogeneic hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk cytogenetics.Herein we review the published data regarding the role of allo-HCT in adults with AML.We searched MEDLINE/PubMed and EMBASE/Ovid.In addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial databases.We discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory AML.Besides the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood.We also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of allo-HCT.Finally we explore recent advances and future possibilities and directions of allo-HCT in AML.Practical therapeutic recommendations have been made where possible based on available data and expert opinion.