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Preclinical development of human cells for potential therapeutic application in neurodegenerative diseases requires that their long-term survival, stability and functional efficacy be studied in animal models of human disease. Here we describe a strategy for long-term immune protection of human fetal and stem cell-derived neural cells transplanted into the adult rat brain, by desensitizing the host rat to similar cells in the neonatal period, without the need for additional immunosuppression.

Fluorescent in-situ hybridization (ISH) to interphase nuclei of human preimplantation embryos has been demonstrated with the X and Y chromosome-specific DNA probes, pBamX7 and pHY2.1, respectively. Assigning the sex on the basis of the number of hybridization signals in the majority of nuclei, the efficiencies with both probes to nuclei from male embryos were considerably higher than those previously reported for pHY2.1 detected by isotopic or conventional non-isotopic methods. Only approximately 15% of nuclei from male embryos failed to hybridize with these probes. With pBamX7, a high incidence (18%) of nuclei with two (or more) signals in embryos classified as males and four signals in a female embryo was observed. In some cases, the double spot nuclei were larger than those with single spots, providing evidence of tetraploidy. The feasibility of using fluorescent ISH for sexing biopsied embryos in couples at risk of X-linked disease and for the preimplantation diagnosis of chromosome abnormalities is discussed.

Reconstruction of CNS circuitry is a major aim of neural transplantation, and is currently being assessed clinically using foetal striatal tissue in Huntington's disease. Recent work suggests that neuronal precursors derived from foetal striatum may have a greater capacity than primary foetal striatum to project to the usual striatal target areas such as the globus pallidus and substantia nigra, raising the possibility that they have a greater potential for circuit reconstruction. However, comparing the reconstructive capacity of the two donor cells types is confounded by the fact that many precursor experiments have been carried out in a xenogeneic background in order to utilize species-specific markers for tracking the donor cells, whereas most primary foetal transplant studies have utilized an allograft paradigm. Thus, differences in immunogenic background could influence the findings; for example, xenogeneic grafts may not recognize host inhibitory signals, thereby encouraging more profuse and extensive projections. We have addressed this issue directly by comparing foetal neural precursor and primary foetal grafts in both allo- and xenograft environments using several labelling techniques, including GFP-transgenic mice and LacZ-labelled cells as donor tissue and iontophoretic injection of the anterograde tracers BDA, neurobiotin and PHA-L in the host. We present clear evidence that foetal neural precursors produce grafts with richer axonal outgrowth than primary foetal grafts, and that this is independent of the immunogenic background. Furthermore, both neural precursor and primary grafts derived from human foetal tissue produced a significantly richer outgrowth than do grafts of mouse donor tissue, which may relate to their large final graft volume and the greater intrinsic potential of human CNS neurons for greater axon elongation.

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To assess the proportion of women found to have rectovaginal endometriosis who underwent a previous laparoscopy with negative findings, a 5-year retrospective observational study was carried out at the University Hospital of Wales, Cardiff UK, from 2001 to 2005. A total of 61 cases with potential symptoms of rectovaginal endometriosis who underwent laparoscopy were identified. Rectovaginal endometriosis was identified in 16 of these cases. Previous laparoscopy was carried out in 33 of these 61 cases. In the group of women found to have rectovaginal endometriosis, 14 cases of rectovaginal endometriosis were not identified by pre-referral laparoscopy. This study supports the anecdotal idea that rectovaginal endometriosis is an often missed diagnosis at the time of laparoscopy. Diagnostic laparoscopy by generalist gynaecologists frequently fails to diagnose rectovaginal endometriosis. The routine use of rectal probes at laparoscopy is recommended to increase diagnostic accuracy.

"Proof-of-principle" that cell replacement therapy works for neurodegeneration has been reported, but only using donor cells collected from fetal brain tissue obtained from surgical terminations of pregnancy. Surgical terminations of pregnancy represent an increasingly limited supply of donor cells due to the tendency towards performing medical termination in much of Europe. This imposes a severe constraint on further experimental and clinical cell transplantation research. Therefore, we explore here the feasibility of using medical termination tissue as a donor source. Products of conception were retrieved from surgical terminations over the last 7 years and from medical terminations over the last 2.5 years. The number of collections that yielded fetal tissue, viable brain tissue, and identifiable brain regions (ganglionic eminence, ventral mesencephalon, and neocortex) were recorded. We studied cell viability, cell physiological properties, and differentiation potential both in vitro and following transplantation into the central nervous system of rodent models of neurodegenerative disease. Within equivalent periods, we were able to collect substantially greater numbers of fetal remains from medical than from surgical terminations of pregnancy, and the medical terminations yielded a much higher proportion of identifiable and dissectible brain tissue. Furthermore, we demonstrate that harvested cells retain the capacity to differentiate into neurons with characteristics appropriate to the region from which they are dissected. We show that, contrary to widespread assumption, medical termination of pregnancy-derived fetal brain cells represent a feasible and more readily available source of human fetal tissue for experimental cell transplantation with the potential for use in future clinical trials in human neurodegenerative disease.

BackgroundIn the UK, 11.8% of expectant mothers undergo an elective caesarean section (ELCS) representing 92 000 births per annum. It is not known to what extent this procedure has an impact on mental well-being in the longer term.AimsTo determine the prevalence and postpartum progression of anxiety and depression symptoms in women undergoing ELCS in Wales.MethodPrevalence of depression and anxiety were determined in women at University Hospital Wales (2015–16; n = 308) through completion of the Edinburgh Postnatal Depression Scale (EPDS; ≥13) and State-Trait Anxiety Inventory (STAI; ≥40) questionnaires 1 day prior to ELCS, and three postpartum time points for 1 year. Maternal characteristics were determined from questionnaires and, where possible, confirmed from National Health Service maternity records.ResultsUsing these criteria the prevalence of reported depression symptoms was 14.3% (95% CI 10.9–18.3) 1 day prior to ELCS, 8.0% (95% CI 4.2–12.5) within 1 week, 8.7% (95% CI 4.2–13.8) at 10 weeks and 12.4% (95% CI 6.4–18.4) 1 year postpartum. Prevalence of reported anxiety symptoms was 27.3% (95% CI 22.5–32.4), 21.7% (95% CI 15.8–28.0), 25.3% (95% CI 18.5–32.7) and 35.1% (95% CI 26.3–44.2) at these same stages. Prenatal anxiety was not resolved after ELCS more than 1 year after delivery.ConclusionsWomen undergoing ELCS experience prolonged anxiety postpartum that merits focused clinical attention.Declaration of interestNone.