No abstract

Myelomeningocele (MMC) is a devastating anomaly with lifelong disability and morbidity. This is the first nonlethal disease as an indication of possible fetal surgery, and currently is the most common disease having undergone open fetal surgery. Although fetal surgical repair alone has been partially improving postnatal long-term clinical outcome, additional innovative strategy to be coupled with should be further investigated. In this regard, we studied the significance of tissue engineering technology as a means of provoking synergistic regeneration of the spinal cord that has been injured due to the associated MMC by the time of fetal anatomical repair. The aim of this report is to evaluate therapeutic feasibility of prenatal direct coverage of the MMC using an adherent sheet-like cluster of cultured myoblasts, the cell sheet. In our study using SD rat as a retinoic-acid-induced model of fetal MMC, a piece of the sheet was directly attached onto the surface of the MMC lesion following anesthesia, laparotomy and hysterotomy. As a result, we could reveal that the cell sheet could histologically seal up the lesion if it was properly kept stuck 4, 6 and 24 hours in utero. In conclusion, the cell sheet, as a part of therapeutic strategy, is likely to work for improving the outcome of correcting fetal MMC surgically.

In recent years, fetal endoscopic tracheal occlusion FETO using a balloon has been clinically employed for promoting prenatal lung growth to ameliorate postnatal respiratory failure caused by severe in utero lung hypoplasia. After a successful FETO, in some limited fetal centers, planned or emergency balloon removal using another fetoscopy is performed to release the tracheal occlusion immediately before delivery. To overcome this additional fetoscopy, we previously reported an innovative simple procedure to remove the occluding balloon by bursting it with a pre-planned sequence of high intensity focused ultrasound HIFU irradiation. In that previous study, which used rabbits euthanized and submerged in degassed water, we in ated the balloon by injecting a mixture of per uorocarbon and ultrasound contrast medium through a fetoscopically-guided catheter. The rate of successful balloon burst and deflation using HIFU irradiation was high enough 100 , but the mode and timing of tracheal reopening i.e., sudden burst or slow shrinkage of the balloon was rather varied and collateral damage to the dermal/tracheal tissue was identi ed in 72.7 of the experimental animals. Accordingly, to standardize the HIFU irradiation sequence and to achieve a reliable and secure balloon burst, we conducted another series of animal experiments in which the mixture of perfluorocarbon was replaced with limonene emulsion D-limonene micelle emulsi ed in physiological saline as the balloon injection uid. In all 6 animals, we succeeded in reopening the airway by achieving an instantaneous and timely balloon burst without de nite skin/tracheal damage. We conclude that HIFU irradiation together with injecting the balloon with limonene emulsion is an improved method for safe tracheal release from a balloon occlusion.