Once their safety is confirmed, human-induced pluripotent stem cells (hiPSCs), which do not entail ethical concerns, may become a preferred cell source for regenerative medicine. Here, we investigated the therapeutic potential of transplanting hiPSC-derived neurospheres (hiPSC-NSs) into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) mice to treat spinal cord injury (SCI). For this, we used a hiPSC clone (201B7), established by transducing four reprogramming factors (Oct3/4, Sox2, Klf4, and cMyc) into adult human fibroblasts. Grafted hiPSC-NSs survived, migrated, and differentiated into the three major neural lineages (neurons, astrocytes, and oligodendrocytes) within the injured spinal cord. They showed both cell-autonomous and noncellautonomous (trophic) effects, including synapse formation between hiPSC-NS-derived neurons and host mouse neurons, expression of neurotrophic factors, angiogenesis, axonal regrowth, and increased amounts of myelin in the injured area. These positive effects resulted in significantly better functional recovery compared with vehicle-treated control animals, and the recovery persisted through the end of the observation period, 112 d post-SCI. No tumor formation was observed in the hiPSC-NS-grafted mice. These findings suggest that hiPSCs give rise to neural stem/progenitor cells that support improved function post-SCI and are a promising cell source for its treatment.stem-cell-based medicine | cell transplantation | neurotrauma | synaptic connection S tem-cell-based approaches, such as the transplantation of neural stem/progenitor cells (NS/PCs), are promising sources of therapies for various central nervous system disorders (1-3). Previous studies reported functional recovery after transplantation of NS/PCs into the injured spinal cord of rodents and nonhuman primates (4-9). Furthermore, recent studies revealed that embryonic stem cells (ESCs) can generate neural cells including NS/PCs (10-12) and oligodendrocyte precursor cells (OPCs) (13,14). Therefore, human ESC-based therapies are moving out of the laboratory and into clinical treatments for spinal cord injury (SCI) (12,13,15). However, the use of human ESC-based therapies is complicated by ethical concerns in certain countries. To avoid the problems associated with ESCs, we previously established induced pluripotent stem cells (iPSCs) from mouse fibroblasts (16, 17) and confirmed the therapeutic potential of iPSC-derived neurospheres (iPSC-NSs) for treating SCI in animal models (18).Here, aiming at human iPSC-based therapies for SCI patients, we examined the therapeutic potential of human iPSC-NSs by transplanting them into nonobese diabetic severe combined immunodeficient (NOD-SCID) SCI model mice. We used a clone from human iPSCs (hiPSCs) that we established from adult human dermal fibroblasts by the retroviral transduction of four reprogramming factors; for the clone used in this study, 201B7, the factors were Oct3/4, Sox2, Klf4, and c-Myc (19). These grafted hiPSC-NSs survived, migrated, and differentiated in...

Objectives: To evaluate the prognosis of monochorionic twins with selective intrauterine growth restriction (sIUGR), classified according to the type of umbilical artery Doppler, under expectant management. Methods: The outcome of 81 cases with isolated sIUGR was evaluated according to a classification based on umbilical artery (UA) Doppler diastolic flow in the IUGR twin (I: present, II: constantly absent/reverse, III: intermittently absent/reverse). Selective feticide was not considered due to legal constraints. Perinatal outcomes included perinatal death and neurological outcome at 6 months of age. Results: From 81 cases with the diagnosis of sIUGR, twin-twin transfusion was diagnosed in 18 cases. This left 63 cases, of which 23 were classified as type I (36.5%), 27 as type II (42.9%) and 13 as type III (20.6%). Intrauterine death occurred in 4.3% (1), 29.6% (8) and 15.4% (2) among IUGR twins, and 4.3% (1), 22.2% (6) and 0.0% (0) among larger twins. Neonatal death occurred in 0.0% (0), 18.5% (5) and 0.0% (0) among IUGR twins, and 0.0% (0), 11.1% (3) and 23.0% (3) among larger twins. Neurological abnormalities at 6 months were found in 4.3% (1), 14.8% (4) and 23.1% (3) in smaller twins and 0.0% (0), 11.1% (3) and 38.5% (5) in larger twins, respectively. Intact survival at 6 months was recorded in 91% (21), 37% (10) and 61% (8) in smaller twins and 95% (22), 55% (15) and 38% (5) in larger twins, respectively. Conclusion: The outcome in monochorionic twins with sIUGR and abnormal umbilical artery Doppler is poor under expectant management. Normal Doppler seems to be associated with a good prognosis.

Previous reports of functional recovery from spinal cord injury (SCI) in rodents and monkeys after the delayed transplantation of neural stem/progenitor cells (NS/PCs) have raised hopes that stem cell therapy could be used to treat SCI in humans. More research is needed, however, to understand the mechanism of functional recovery. Oligodendrocytes derived from grafted NS/PCs remyelinate spared axons in the injured spinal cord. Here, we studied the extent of this remyelination's contribution to functional recovery following contusive SCI in mice. To isolate the effect of remyelination from other possible regenerative benefits of the grafted cells, NS/PCs obtained from myelin-deficient shiverer mutant mice (shi-NS/PCs) were used in this work alongside wild-type NS/PCs (wt-NS/PCs). shi-NS/PCs behaved like wt-NS/PCs in vitro and in vivo, with the exception of their myelinating potential. shi-NS/ PC-derived oligodendrocytes did not express myelin basic protein in vitro and formed much thinner myelin sheaths in vivo compared with wt-NS/PC-derived oligodendrocytes. The transplantation of shi-NS/PCs promoted some locomotor and electrophysiological functional recovery but significantly less than that afforded by wt-NS/PCs. These findings establish the biological importance of remyelination by graft-derived cells for functional recovery after the transplantation of NS/PCs into the injured spinal cord.

FLS leads to high survival rates and low neurological morbidity for fetuses in TTTS. FLS is an effective therapeutic option for TTTS before 26 weeks of gestation. Preoperative Doppler findings of the umbilical artery and the ductus venosus are useful in predicting prognosis following FLS.

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To investigate potential cures for spinal cord injury (SCI), several researchers have transplanted neural stem/ progenitor cells (NS/PCs) into the injured spinal cord by different procedures, including intralesional (IL), intrathecal (IT), and intravenous (IV) injection. However, there are no reports quantifying or comparing the number of cells successfully transplanted to the lesion site by each procedure in vivo. The purpose of the present study was to determine the optimal method of cell transplantation to the SCI site in terms of grafted cell survival and safety. For this purpose, we developed mouse NS/PCs that expressed a novel Venusluciferase fusion protein that enabled us to detect a minimum of 1,000 grafted cells in vivo by bioluminescence imaging (BLI). After inducing contusive SCI at the T10 level in mice, NS/PCs were transplanted into the injured animals three different ways: by IL, IT, or IV injection. Six weeks after the transplantation, BLI analysis showed that in the IL group, the luminescence intensity of the grafted cells had decreased to about 10% of its initial level, and appeared at the site of injury. In the IT group, the luminescence of the grafted cells, which was distributed throughout the entire subarachnoid space immediately after transplantation, was detected at the injured site 1 week later, and by 6 weeks had gradually decreased to about 0.3% of its initial level. In the IV group, no grafted cells were detected at the site of injury, but all of these mice showed luminescence in the bilateral chest, suggesting pulmonary embolism. In addition, one third of these mice died immediately after the IV injection. In terms of grafted cell survival and safety, we conclude that the IL application of NS/PCs is the most effective and feasible method for transplanting NS/PCs into the SCI site. INTRODUCTIONstem/progenitor cell (NS/PC) transplantation is considered one of the most promising, because the transplantation of NS/PCs into rodent SCI models (13,15,27,42, Because the adult central nervous system (CNS) has little potential for regeneration, spinal cord injury (SCI) 44,48) and of human neural stem/progenitor cells (NS/ PCs) into a marmoset SCI model (28) have been shown usually results in severe damage, leading to paraplegia, tetraplegia, or worse. Several strategies have been used to promote functional recovery. From the viewpoint of clinical trials, it is critical to to develop new therapies that would allow patients to regain the use of their paralyzed limbs. Because cell determine how best to apply cells to the injured spinal cord. Three application methods for cell transplantation transplantation is one of the potential therapies, various kinds of cells have been used as the transplantation source for SCI are used: intralesional (IL), intrathecal (IT), and intravenous (IV). Some previous studies have sought to for SCI (14,18,(32)(33)(34)37,38,46 compare different cell transplantation methods for treatcentrated virus was 1 × 10 8 to 2 × 10 8 transducing units per milliliter (TU/ml) when...

Objective To evaluate the incidence, risk factors and consequences of intrauterine fetal demise (IUFD) of at least one twin in twin-to-twin transfusion syndrome (TTTS) treated by laser.Design Retrospective analysis.Setting Experience of a single centre between 1999 and 2004.Population A subgroup of 45 cases with fetal demise of one or both twins from a series of 120 cases of TTTS treated by laser.Methods All cases were entered prospectively into a dedicated database and the results were analysed retrospectively.Main outcome measures Fetal demise prognostic factors, survival, fetal anaemia, brain lesions, neonatal death and intact survival.Results IUFD of one twin occurred in 40 of 120 cases (19 donors and 21 recipients). IUFD of both twins occurred in another five cases. From these 40 cases, miscarriage occurred in two and pregnancy termination was requested in another two cases because of antenatal brain lesions. Two neonates died and two presented severe morbidity, survivors were therefore neurologically normal at 6-44 months of life in 89% (32/36) of the cases. Univariate analysis showed that preoperative abnormal umbilical artery Doppler in the donor before laser treatment and in the recipient following laser treatment was associated with their demise. Incomplete coagulation was suspected in cases where anaemia or cerebral lesions developed following the death of the first twin (10).Conclusions IUFD of one or both twins occurred in 45 of 120 (38%) cases of severe TTTS treated by laser. In these, separation of the placental circulations was incomplete in at least 22% (10/45) of the cases. Umbilical artery Doppler abnormalities before laser were found to be risk factors for the donors' demise following the procedure.

Objectives The aim of this study was to evaluate the use of ultrasound assessment to predict risk of mortality in expectantly managed monochorionic twin fetuses with selective intrauterine growth restriction (sIUGR). Methods