1.
Small-molecule nicotinamide for ex vivo expansion of umbilical cord blood.
Islam, P, Horwitz, ME
Experimental hematology. 2019;:11-15
Abstract
Umbilical cord blood transplant is an alternative graft source for patients lacking a human leukocyte antigen-matched donor; however, delayed engraftment times have historically resulted in transplant-related morbidity and mortality from complications such as infections and ineffective hematopoiesis. Recent advances in ex vivo expansion techniques have successfully augmented the initial cell dose delivered from an umbilical cord blood graft, leading to improved immune reconstitution, durable hematopoiesis, decreased transplant-related morbidity and mortality, and better outcomes. Herein we review the data for existing and developing ex vivo expansion techniques, with a focus on the preclinical and clinical data for nicotinamide-mediated cord blood expansion across both malignant and benign hematologic indications.
2.
A Low Glycaemic Index Diet in Pregnancy Induces DNA Methylation Variation in Blood of Newborns: Results from the ROLO Randomised Controlled Trial.
Geraghty, AA, Sexton-Oates, A, O'Brien, EC, Alberdi, G, Fransquet, P, Saffery, R, McAuliffe, FM
Nutrients. 2018;(4)
Abstract
The epigenetic profile of the developing fetus is sensitive to environmental influence. Maternal diet has been shown to influence DNA methylation patterns in offspring, but research in humans is limited. We investigated the impact of a low glycaemic index dietary intervention during pregnancy on offspring DNA methylation patterns using a genome-wide methylation approach. Sixty neonates were selected from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet to prevent macrosomia) study: 30 neonates from the low glycaemic index intervention arm and 30 from the control, whose mothers received no specific dietary advice. DNA methylation was investigated in 771,484 CpG sites in free DNA from cord blood serum. Principal component analysis and linear regression were carried out comparing the intervention and control groups. Gene clustering and pathway analysis were also explored. Widespread variation was identified in the newborns exposed to the dietary intervention, accounting for 11% of the total level of DNA methylation variation within the dataset. No association was found with maternal early-pregnancy body mass index (BMI), infant sex, or birthweight. Pathway analysis identified common influences of the intervention on gene clusters plausibly linked to pathways targeted by the intervention, including cardiac and immune functioning. Analysis in 60 additional samples from the ROLO study failed to replicate the original findings. Using a modest-sized discovery sample, we identified preliminary evidence of differential methylation in progeny of mothers exposed to a dietary intervention during pregnancy.
3.
Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.
Shah, N, Li, L, McCarty, J, Kaur, I, Yvon, E, Shaim, H, Muftuoglu, M, Liu, E, Orlowski, RZ, Cooper, L, et al
British journal of haematology. 2017;(3):457-466
-
-
Free full text
-
Abstract
Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m2 on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 106 , 1 × 107 , 5 × 107 and 1 × 108 CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D+ /NKp30+ ). These data warrant further development of this novel cellular therapy.
4.
Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses.
Akhtar, E, Mily, A, Haq, A, Al-Mahmud, A, El-Arifeen, S, Hel Baqui, A, Roth, DE, Raqib, R
Nutrition journal. 2016;(1):75
Abstract
BACKGROUND Antenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear. METHOD To assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo from 26 to 29 weeks of gestation to delivery. In a subset of participants (n = 80), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants, lymphocyte gene expression profiles were analyzed by PCR array. RESULT In supplemented group, increased concentrations of IL-10 (P < 0.000) and TNF-α (P = 0.05) with iCD3/iCD28 stimulation and IFN-γ (p = 0.05) with PHA stimulation were obtained compared to placebo group. No differences in the gene expression profile were noted between the two groups. However, PHA stimulation significantly induced the expression of genes encoding Th1 and Th2 cytokines and down-regulated a number of genes involved in T-cell development, proliferation and differentiation of B cells, signal transduction pathway, transcriptional regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD group). CONCLUSION Third-trimester high-dose vitD3 supplementation in healthy pregnant women had balanced effects on biomarkers of cord blood Th1 and Th2 responses. TRIAL REGISTRATION ClinicalTrials.gov ( NCT01126528 ).