Transplantation of Human-Fetal-Spinal-Cord-Derived NPCs Primed with a Polyglutamate-Conjugated Rho/Rock Inhibitor in Acute Spinal Cord Injury.

Neural precursor cell (NPC) transplantation represents a promising therapy for treating spinal cord injuries (SCIs); however, despite successful results obtained in preclinical models, the clinical translation of this approach remains challenging due, in part, to the lack of consensus on an optimal cell source for human neuronal cells. Depending on the cell source, additional limitations to NPC-based therapies include high tumorigenic potential, alongside poor graft survival and engraftment into host spinal tissue. We previously demonstrated that NPCs derived from rat fetal spinal cords primed with a polyglutamate (PGA)-conjugated form of the Rho/Rock inhibitor fasudil (PGA-SS-FAS) displayed enhanced neuronal differentiation and graft survival when compared to non-primed NPCs. We now conducted a similar study of human-fetal-spinal-cord-derived NPCs (hfNPCs) from legal gestational interruptions at the late gestational stage, at 19-21.6 weeks. In vitro, expanded hfNPCs retained neural features, multipotency, and self-renewal, which supported the development of a cell banking strategy. Before transplantation, we established a simple procedure to prime hfNPCs by overnight incubation with PGA-SS-FAS (at 50 µM FAS equiv.), which improved neuronal differentiation and overcame neurite-like retraction after lysophosphatidic-acid-induced Rho/Rock activation. The transplantation of primed hfNPCs into immune-deficient mice (NU(NCr)-Foxn1nu) immediately after the eighth thoracic segment compression prompted enhanced migration of grafted cells from the dorsal to the ventral spinal cord, increased preservation of GABAergic inhibitory Lbx1-expressing and glutamatergic excitatory Tlx3-expressing somatosensory interneurons, and elevated the numbers of preserved, c-Fos-expressing, activated neurons surrounding the injury epicenter, all in a low percentage. Overall, the priming procedure using PGA-SS-FAS could represent an alternative methodology to improve the capabilities of the hfNPC lines for a translational approach for acute SCI treatment.

The prevalence of congenital varicella syndrome after a maternal infection, but before 20 weeks of pregnancy: a prospective cohort study.

OBJECTIVE: To describe the prevalence of congenital varicella syndrome (CVS) within the population of presumably infected pregnant women. METHODS: From 1993 to 2006, all women who presented vesicular rash or a suspicious contact were referred and evaluated in a special unit at our center. Those with residual immunity or were serologically negative were precluded from this study. Positive IgM cases underwent monthly ultrasound scans (US), fetal blood (FB) sampling (including IgM anti VZV and virus culture). Amniotic fluid sample for PCR was added to the diagnosis of positive IgM cases after 1997. RESULTS: A total of 276, of the 566 consulted women, tested positive for IgM anti VZV. Seventeen (6%) were excluded because of an unadvised termination of pregnancy and seven (2.55%) miscarried. Only seven (2.7%) were considered highly likely to have a VZV fetal infection. One case showed positive IgM in FB but developed normally. Another fetus showed positive PCR and infection was confirmed post TOP. Four cases that underwent TOP and histochemistry confirmed no more cases. Complete post-natal follow-up was carried out. The asymptomatic infected child grew healthy until the completion of screening tests when it reached 5 years old. CONCLUSION: The fetal infection rate in this cohort was 0.8%, but the best expected prevalence of CVS, according to our findings, should be 0.39% among infected women. This data should be considered and used during parental counselling.

Use of 3-dimensional sonography for prenatal evaluation and follow-up of fetal goitrous hypothyroidism.

OBJECTIVE: Fetal goitrous hypothyroidism is a rare and potentially lethal condition. Consequently, its early diagnosis and treatment improve prognosis. Thyroid hormone measurement in either fetal serum or amniotic fluid implies important risks. Here we present a fetal goiter and the follow-up procedure, both done by the traditional method and by using 3-dimensional power Doppler (3DPD) imaging and virtual organ computer-aided analysis (VOCAL). METHODS: A single well-documented case of fetal goiter was followed weekly from 22 weeks until delivery. Amniocentesis for thyrotropin (TSH) and free thyroxine (T(4)) measurement as well as levothyroxine injections were performed at every control. In addition to amniocentesis, every control involved a sonographic evaluation, which included standard measurements of the gland and the capture of volume image sets in gray scale and 3DPD. Volume calculation of the gland was done using VOCAL software. Vascularization of the gland was evaluated by the vascularization index (VI) included in the software. RESULTS: With treatment, TSH levels decreased progressively until normalization. Free T(4) levels increased toward the end of gestation. Sonographic measurements of the gland volume to estimated fetal weight ratio decreased across treatment as levels of TSH did. The VI clearly depicted the vascular regression of the goiter, decreasing throughout treatment in a consistent way until 24 hours before delivery. CONCLUSIONS: Gray scale and 3DPD evaluations of the thyroid gland have been validated under similar circumstances and might be reliable complements to the invasive methods used in the management of this fetal condition.