Biodistribution of allogenic umbilical cord-derived mesenchymal stromal cells after fetal repair of myelomeningocele in an ovine model

Abstract Background Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of MMC provides a significant benefit compared to surgery at birth. Mesenchymal stromal cell (MSC) therapy as an adjuvant treatment for prenatal surgery showed promising results in animal experiments which could be considered for clinical use in human fetuses. Despite numerous reassuring studies on the safety of MSCs administration in humans, no study focused on MSCs biodistribution after a local MSCs graft on the fetal spinal cord. Aim The purpose of our study was to assess the biodistribution of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) at birth in lambs who had a prenatal myelomeningocele repair using a fibrin patch seeded with allogenic UC-MSCs. Methods After isolation, UC-MSCs were tagged using a green fluorescent protein (GFP)-containing lentiviral vector. MMC defects were surgically created at 75 days of gestation and repaired 15 days later using UC-MSCs patch. Lambs were delivered at 142 days and sacrificed. DNA extraction was performed among biopsies of the different organs and q-PCR analysis was used to detect the expression of GFP (GFP DNA coding sequence). Results In our 6 surviving lambs grafted with UC-MSCs, GFP lentivirus genomic DNA was not detected in the organs. Conclusion These reassuring data will support translational application in humans, especially since the first human clinical trial using mesenchymal stromal cells for in-utero treatment of MMC started recently in U.S.A

Effect of intravenous immunoglobulins to postpone the gestational age of first intrauterine transfusion in very severe red blood cell alloimmunization: A case-control study

Background: Early intrauterine transfusion (IUT) is associated with a higher risk of fetal loss. Our objective was to evaluate the efficiciency of intravenous immunoglobulins (IVIG) to postpone the gestational age at first IUT beyond 20 weeks of gestation (WG) compared to the previous pregnancy in case of very severe red blood cell (RBC) alloimmunization. Study design and methods: Very severe RBC alloimmunization was defined by a high titer of antibodies and a previous pregnancy complicated by a first IUT before 24 WG and/or perinatal death directly related to alloimmunization. We performed a single-center case-control study. Cases and controls were patients respectively treated with weekly IVIG infusions started before 13 WG, and without. Results: Twenty cases and 21 controls were included. Gestational age (GA) at first IUT was postponed after 20 WG in 18/20 (90 %) of patients treated with IVIG and in 15/21 (71 %) in the control group (p = 0.24). Compared to the previous pregnancy, the GA at first IUT was postponed by a median of 22 [+11; +49] days in the IVIG group and occurred in average 2 days earlier [-17 ; +12] in the non-treated group (p = 0.02). There was no difference between number of IUT and need for exchange-transfusion. IVIG treatment was associated with a significant decrease of antibodies' quantitation. Conclusion: In our series, IVIG tends to differ first IUT beyond 20 WG and have a significant effect in postponing the gestational age of the first IUT in patients with very severe RBC alloimmunization

Pain experienced by infants and toddlers at urine collection bag removal: A randomized, controlled, clinical trial

International audienceBACKGROUND:In pre-continent children, collection bags are frequently used as a first-line option to obtain a urine specimen. This practice, acknowledged by several guidelines for the step of UTI screening, is driven by a perception of the technique as being more convenient and less painful. However, our own experience led us to consider bag removal as a painful experience.OBJECTIVE:Our aim was to determine whether the use of an oleo-calcareous liniment to aid bag removal reduced the acute pain expressed by young children.METHODS:This prospective, randomized, controlled, single blind study was carried out in two emergency pediatrics departments. Pre-continent children aged 0-36 months admitted with an indication for urine testing were eligible for the study. Urine for dipstick test screening was obtained using a collection bag. At micturition, the patients were randomized into bag removal with (intervention group) or without (control group) liniment. Bag removal was recorded on video in such a manner as to permit independent assessments of pain by two evaluators blinded to group allocation. Pain was assessed using the FLACC scale.FINDINGS:135 patients were analyzed: 70 in the intervention group and 65 in the control group. The median FLACC scores [interquartile range] for the intervention and control groups, respectively 4.0 [2.0-7.0] and 4.0 [3.0-7.0], did not differ significantly (p = 0.5). A FLACC score ≥4 was obtained for 56% of the patients and a score ≥7 for 28%.CONCLUSION:Removal of urine collection bags caused moderate to severe pain in half of the children included. The use of an oleo-calcareous liniment did not reduce this induced pain

In utero treatment of myelomeningocele with allogenic umbilical cord-derived mesenchymal stromal cells in an ovine model

Ce manuscrit est mis à disposition sous la licence d'utilisation Elsevier https://www.elsevier.com/open-access/userlicense/1.0/ International audiencePURPOSE OF THE STUDY: The purpose of our study was to investigate the effects of ovine umbilical cord-derived mesenchymal stromal cells (UC-MSCs) seeded in a fibrin patch as an adjuvant therapy for fetal myelomeningocele repair in the ovine model. MATERIALS AND METHODS: MMC defects were surgically created at 75 days of gestation and repaired 15 days later with UC-MSCs patch or an acellular patch. At birth, motor function, tail movements, and voiding abilities were recorded. Histological and immunohistochemical analysis included study of MMC defect's healing, spinal cord, UC-MSCs survival, and screening for tumors. RESULTS: Six lambs were born alive in each group. There was no difference between the two groups on the median sheep locomotor rating score but all lambs in the control group had a score between lower than 3 compared to 50% in UC-MSCs group. There were more lambs with tail movements and voiding ability in UC-MSCs group (83% vs 0% and 50% vs 0%, respectively). gray matter area and large neurons density were higher in UC-MSCs group (2.5 vs 0.8 mm2 and 19.3 vs 1.6 neurons/mm2 of gray matter, respectively). Fibrosis thickness at the myelomeningocele scar level was reduced in UC-MSCs group (1269 µm vs 2624 µm). No tumors were observed. CONSLUSION : Fetal repair of myelomeningocele using allogenic UC-MSCs patch provides a moderate improvement in neurological functions, gray matter and neuronal preservation and prevented from fibrosis development at the myelomeningocele scar leve

Prophylaxie préexposition au VIH (PrEP) en médecine générale : existe-t-il des freins ?

International audiencePurpose of the studyThe purpose of our study was to investigate the effects of ovine umbilical cord-derived mesenchymal stromal cells (UC-MSCs) seeded in a fibrin patch as an adjuvant therapy for fetal myelomeningocele repair in the ovine model.Materials and methodsMMC defects were surgically created at 75 days of gestation and repaired 15 days later with UC-MSCs patch or an acellular patch. At birth, motor function, tail movements, and voiding abilities were recorded. Histological and immunohistochemical analysis included study of MMC defect's healing, spinal cord, UC-MSCs survival, and screening for tumors.ResultsSix lambs were born alive in each group. There was no difference between the two groups on the median sheep locomotor rating score but all lambs in the control group had a score between lower than 3 compared to 50% in UC-MSCs group. There were more lambs with tail movements and voiding ability in UC-MSCs group (83% vs 0% and 50% vs 0%, respectively). gray matter area and large neurons density were higher in UC-MSCs group (2.5 vs 0.8 mm2 and 19.3 vs 1.6 neurons/mm2 of gray matter, respectively). Fibrosis thickness at the myelomeningocele scar level was reduced in UC-MSCs group (1269 µm vs 2624 µm). No tumors were observed.ConclusionFetal repair of myelomeningocele using allogenic UC-MSCs patch provides a moderate improvement in neurological functions, gray matter and neuronal preservation and prevented from fibrosis development at the myelomeningocele scar level