Media(ted) fabrications: How the science-media symbiosis helped ‘sell’ cord banking

This paper considers the problematic role of the science–media symbiosis in the dissemination of misleading and emotionally manipulative information regarding services offered by CordBank, New Zealand's only umbilical cord blood banking facility. As this case study illustrates, the growing reliance of health and science reporters on the knowledge capital of medical specialists, biogenetic researchers, and scientists potentially enhances the ability of ‘expert’ sources to set the agenda for media representations of emerging medical and scientific developments, and may undermine the editorial independence of journalists and editors, many of whom in this case failed to critically evaluate deeply problematic claims regarding the current and future benefits of cord banking. Heavy reliance on established media frames of anecdotal personalization and technoboosterism also reinforced a proscience journalistic culture in which claims by key sources were uncritically reiterated and amplified, with journalistic assessments of the value of cord banking emphasizing potential benefits for individual consumers. It is argued that use of these media frames potentially detracts from due consideration of the broader social, ethical, legal, and health implications of emerging biomedical developments, along with the professional, personal, and increasingly also financial interests at stake in their public promotion, given the growing commercialization of biogenetic technologies

Classification of stillbirths is an ongoing dilemma

Aim: To compare different classification systems in a cohort of stillbirths undergoing a comprehensive workup; to establish whether a particular classification system is most suitable and useful in determining cause of death, purporting the lowest percentage of unexplained death. Methods: Cases of stillbirth at gestational age 22–41 weeks occurring at the Department of Gynecology and Obstetrics of Foggia University during a 4 year period were collected. The World Health Organization (WHO) diagnosis of stillbirth was used. All the data collection was based on the recommendations of an Italian diagnostic workup for stillbirth. Two expert obstetricians reviewed all cases and classified causes according to five classification systems. Results: Relevant Condition at Death (ReCoDe) and Causes Of Death and Associated Conditions (CODAC) classification systems performed best in retaining information. The ReCoDe system provided the lowest rate of unexplained stillbirth (14%) compared to de Galan-Roosen (16%), CODAC (16%), Tulip (18%), Wigglesworth (62%). Conclusion: Classification of stillbirth is influenced by the multiplicity of possible causes and factors related to fetal death. Fetal autopsy, placental histology and cytogenetic analysis are strongly recommended to have a complete diagnostic evaluation. Commonly employed classification systems performed differently in our experience, the most satisfactory being the ReCoDe. Given the rate of “unexplained” cases, none can be considered optimal and further efforts are necessary to work out a clinically useful system

Influence of a Concurrent Exercise Training Intervention during Pregnancy on Maternal and Arterial and Venous Cord Serum Cytokines: The GESTAFIT Project

The aim of the present study was to analyze the influence of a supervised concurrent exercise-training program, from the 17th gestational week until delivery, on cytokines in maternal (at 17th and 35th gestational week, and at delivery) and arterial and venous cord serum. Fifty-eight Caucasian pregnant women (age: 33.5 +/- 4.7 years old, body mass index: 23.6 +/- 4.1kg/m(2)) from the GESTAFIT Project (exercise (n = 37) and control (n = 21) groups) participated in this quasi-experimental study (per-protocol basis). The exercise group followed a 60-min 3 days/week concurrent (aerobic-resistance) exercise-training from the 17th gestational week to delivery. Maternal and arterial and venous cord serum cytokines (fractalkine, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha) were assessed using Luminex xMAP technology. In maternal serum (after adjusting for the baseline values of cytokines), the exercise group decreased TNF-alpha (from baseline to 35th week, p = 0.02), and increased less IL-1 beta (from baseline to delivery, p = 0.03) concentrations than controls. When adjusting for other potential confounders, these differences became non-significant. In cord blood, the exercise group showed reduced arterial IL-6 and venous TNF-alpha (p = 0.03 and p = 0.001, respectively) and higher concentrations of arterial IL-1 beta (p = 0.03) compared to controls. The application of concurrent exercise-training programs could be a strategy to modulate immune responses in pregnant women and their fetuses. However, future research is needed to better understand the origin and clearance of these cytokines, their role in the maternal-placental-fetus crosstalk, and the influence of exercise interventions on them

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases

Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.

Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel-treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase-2 expression at week 1. Histologically, significantly more MSC-treated wounds were categorized as pro-healing than pro-inflammatory. Wound area was significantly affected by treatment: MSC-injected wounds were consistently smaller than gel-treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. Stem Cells Translational Medicine 2018;7:98-108

Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

Evaluation of the cell viability of human Wharton's jelly stem cells for use in cell therapy

Human umbilical cord Wharton's jelly stem cells (HWJSCs) are gaining attention as a possible clinical source of mesenchymal stem cells for cell therapy and tissue engineering due to their high accessibility, expansion potential, and plasticity. We employed a combination of highly sensitive techniques to determine the average cell viability levels and proliferation capabilities of 10 consecutive cell passages of cultured HWJSCs and then used RNA microarrays to identify genes associated with changes in cell viability levels. We found an initial decrease in cell viability from the first to the third cell passage followed by an increase until the sixth passage and a final decrease from the sixth to tenth cell passages. The highest cell viability levels corresponded to the fifth and sixth passages. The intracellular ionic contents of potassium, sodium, and chlorine suggest that the lower cell viability levels at passages 2, 3, and 8-10 may be associated with apoptotic cell death. In fact, gene expression analysis revealed that the average cell viability was significantly associated with genes with a function in apoptotic cell death, especially pro-apoptotic FASTKD2, BNIP3L genes and anti-apoptotic TNFAIP8 and BCL2L2 genes. This correlation with both pro-apoptotic and anti-apoptotic genes suggests that there may be a complex live-death equilibrium in cultured HWJSCs kept in culture for multiple cell passages. In this study, the highest cell viability levels corresponded to the fifth and sixth HWJSC passages, suggesting that these passages should be preferentially employed in cell therapy or tissue engineering protocols using this cell type

INTELLIGENT TECHNIQUES FOR HANDLING UNCERTAINTY IN THE ASSESSMENT OF NEONATAL OUTCOME

Objective assessment of the neonatal outcome of labour is important, but it is a difficult and challenging problem. It is an invaluable source of information which can be used to provide feedback to clinicians, to audit a unit's overall performance, and can guide subsequent neonatal care. Current methods are inadequate as they fail to distinguish damage that occurred during labour from damage that occurred before or after labour. Analysis of the chemical acid-base status of blood taken from the umbilical cord of an infant immediately after delivery provides information on any damage suffered by the infant due to lack of oxygen during labour. However, this process is complex and error prone, and requires expertise which is not always available on labour wards. A model of clinical expertise required for the accurate interpretation of umbilical acid-base status was developed, and encapsulated in a rule-based expert system. This expert system checks results to ensure their consistency, identifies whether the results come from arterial or venous vessels, and then produces an interpretation of their meaning. This 'crisp' expert system was validated, verified and commercially released, and has since been installed at twenty two hospitals all around the United Kingdom. The assessment of umbilical acid-base status is characterised by uncertainty in both the basic data and the knowledge required for its interpretation. Fuzzy logic provides a technique for representing both these forms of uncertainty in a single framework. A 'preliminary' fuzzy-logic based expert system to interpret error-free results was developed, based on the knowledge embedded in the crisp expert system. Its performance was compared against clinicians in a validation test, but initially its performance was found to be poor in comparison with the clinicians and inferior to the crisp expert system. An automatic tuning algorithm was developed to modify the behaviour of the fuzzy model utilised in the expert system. Sub-normal membership functions were used to weight terms in the fuzzy expert system in a novel manner. This resulted in an improvement in the performance of the fuzzy expert system to a level comparable to the clinicians, and superior to the crisp expert system. Experimental work was carried out to evaluate the imprecision in umbilical cord acid-base parameters. This information, in conjunction with fresh knowledge elicitation sessions, allowed the creation of a more comprehensive fuzzy expert system, to validate and interpret all acid-base data. This 'integrated' fuzzy expert system was tuned using the comparison data obtained previously, and incorporated vessel identification rules and interpretation rules, with numeric and linguistic outputs for each. The performance of each of the outputs was evaluated in a rigorous validation study. This demonstrated excellent agreement with the experts for the numeric outputs, and agreement on a par with the experts for the linguistic outputs. The numeric interpretation produced by the fuzzy expert system is a novel single dimensional measure that accurately represents the severity of acid-base results. The development of the crisp and fuzzy expert systems represents a major achievement and constitutes a significant contribution to the assessment of neonatal outcome.Plymouth Postgraduate Medical Schoo

Antimicrobial peptide LL-37 and recombinant human mannose-binding lectin express distinct age- and pathogen-specific antimicrobial activity in human newborn cord blood in vitro

Background: There is a need to prevent and treat infection in newborns. One approach is administration of antimicrobial proteins and peptides (APPs) such as LL-37, a membrane-active cathelicidin antimicrobial peptide, and mannose-binding lectin (MBL), a pattern-recognition protein that binds to microbial surface polysaccharides resulting in opsonization and complement activation. Low plasma/serum levels of LL-37 and of MBL have been correlated with infection and exogenous administration of these agents may enhance host defense. Methods: The antimicrobial activity of LL-37 (15 µg/ml) or rMBL (0.5, 2 and 10 µg/ml) was tested in hirudin-anticoagulated preterm and term human cord blood (N = 12-14) against Staphylococcus aureus (SA) USA 300 (2x10 4 CFU/ml), Staphylococcus epidermis (SE) 1457 (2x10 4 CFU/ml) and Candida albicans (CA) SC5314 (1x10 4 CFU/ml). After incubation (1, 45, or 180 min), CFUs were enumerated by plating blood onto agar plates. Supernatants were collected for measurement of MBL via ELISA. Results: Preterm cord blood demonstrated impaired endogenous killing capacity against SA and SE compared to term blood. Addition of LL-37 strongly enhanced antimicrobial/antifungal activity vs SA, SE and CA in term blood and SE and CA in preterm blood. By contrast, rMBL showed modest fungistatic activity vs CA in a sub-analysis of term newborns with high basal MBL levels. Baseline MBL levels varied within preterm and term cohorts with no correlation to gestational age. In summary, exogenous LL-37 demonstrated significant antimicrobial activity against SA, SE and CA in term and SE and CA in preterm human blood tested in vitro. rMBL demonstrated modest antifungal activity in term cord blood of individuals with high baseline MBL levels. Conclusions: To the extent that our in vitro results predict the effects of APPs in vivo, development of APPs for prevention and treatment of infection should take into account host age as well as the target pathogen

Advances and challenges in umbilical cord blood and tissue bioprocessing: procurement and storage

Umbilical cord tissue and blood is banked to complement the rapidly advancing field of tissue engineering and regenerative medicine for both autologous and allogeneic therapeutic applications. Whilst many problems concerning the use of the hematopoietic and multipotential mesenchymal stromal cells contained therein may be addressed through the future development of GMP-compliant manufacturing strategies, collection and bioprocessing of these tissues can be optimised in the present to maximise clinical outcomes. In this review, we describe current procurement, processing and storage approaches for umbilical cord blood and tissue; current challenges and how these may be met to augment translation and use of therapeutics harnessing their derivatives