Experimental human fetal neural progenitor cell (hfNPC) transplantation has proven to be a promising therapeutic approach after traumatic brain injury (TBI). However, the long-term efficacy and safety, which are both highly important for clinical translation of this approach, have thus far not been investigated. This study investigated the effect of local (L, 1 × 10(5) cells) and systemic (S, 5 × 10(5) cells) administration of PKH-26-labeled pre-differentiated hfNPCs over a period of 12 weeks, beginning 24 h after severe controlled cortical impact TBI in Sprague-Dawley rats. Accelerating rotarod testing revealed a trend toward functional improvement beginning 1 week after transplantation, and persisting until the end of the experiment. The traumatic lesion volume as quantified by magnetic resonance imaging was smaller in both treatment groups compared to control (C) animals (C = 54.50 mm(3), L = 32 mm(3), S = 37.50 mm(3)). Correspondingly, neuronal (NeuN) staining showed increased neuronal survival at the border of the lesion in both transplanted groups (S = 92.4%; L = 87.2%; 72.5%). Histological analysis of the brain compartments revealed transiently increased angiogenesis and reduced astroglial reaction during the first 4 weeks post-transplantation. PKH-26-positive cells were detected exclusively after local transplantation without any evidence of tumor formation. However, graft differentiation was seen only in very rare cases. In conclusion, transplantation of hfNPCs improved the long-term functional outcome after TBI, diminished trauma lesion size, and increased neuronal survival in the border zone of the lesion. This therapeutic effect was not likely due to cell replacement, but was associated with transiently increased angiogenesis and reduced astrogliosis.

We report on five sibs affected by congenital microcephaly, growth retardation, sloping forehead, bitemporal grooving and micrognathia. Generalized tonic-clonic seizures started very early in life. Postnatal brain computerized tomography (CT) presented cortical band-like calcification, calcification of basal ganglia and brain stem while brain magnetic resonance imaging (MRI) revealed abnormal gyral pattern, marked loss of white matter, dysplastic ventricles, polymicrogyria, hypogenesis of corpus callosum and cerebellar hypoplasia. No abnormalities of the internal organs, eye, or skeleton were found to be associated with this syndrome. Fetal Magnetic resonance imaging helped reaching the diagnosis in utero in one patient. Three patients died in the first years of life while the others within days after birth preceded by high fever and status epilepticus. These patients present many overlapping features with pseudo TORCH syndrome, however, the imaging findings are quite different. We propose that the distinct pattern in these sibs constitutes genetic disorder of microcephaly, developmental brain malformation and intracranial calcification of likely autosomal recessive inheritance.

2After traumatic brain injury (TBI), secondary injuries develop, including neuro-inflammatory 3 processes that contribute to long-lasting impairments. These secondary injuries represent computed tomography to image the neuro-inflammatory response after stroke. In this study, 10we used the same tracer in a rat model of TBI to determine changes in TSPO expression. 11Adult Sprague-Dawley rats were subjected to moderate Controlled-Cortical-Impact injury at 12 the M1 motor cortex, and sacrificed at 6h, 24h, 72h, and 28 days post-surgery. TSPO

BACKGROUND: Cell therapies offer a promising potential in promoting bone regeneration. Stem cell therapy presents attractive care modality in treating degenerative conditions or tissue injuries. The rationale behind this is both the expansion potential of stem cells into a large cell population size and its differentiation abilities into a wide variety of tissue types, when given the proper stimuli. A progenitor stem cell is a promising source of cell therapy in regenerative medicine and bone tissue engineering. AIM: This study aimed to compare the osteogenic differentiation and regenerative potentials of human mesenchymal stem cells derived from human bone marrow (hBM-MSCs) or amniotic fluid (hAF-MSCs), both in vitro and in vivo studies. SUBJECTS AND METHODS: Human MSCs, used in this study, were successfully isolated from two human sources; the bone marrow (BM) and amniotic fluid (AF) collected at the gestational ages of second or third trimesters. RESULTS: The stem cells derived from amniotic fluid seemed to be the most promising type of progenitor cells for clinical applications. In a pre-clinical experiment, attempting to explore the therapeutic application of MSCs in bone regeneration, Rat lumbar spines defects were surgically created and treated with undifferentiated and osteogenically differentiated MSCs, derived from BM and second trimester AF. Cells were loaded on gel-foam scaffolds, inserted and fixed in the area of the surgical defect. X-Ray radiography follows up, and histopathological analysis was done three-four months post- operation. The transplantation of AF-MSCs or BM-MSCs into induced bony defects showed promising results. The AF-MSCs are offering a better healing effect increasing the likelihood of achieving successful spinal fusion. Some bone changes were observed in rats transplanted with osteoblasts differentiated cells but not in rats transplanted with undifferentiated MSCs. Longer observational periods are required to evaluate a true bone formation. The findings of this study suggested that the different sources; hBM-MSCs or hAF-MSCs exhibited remarkably different signature regarding the cell morphology, proliferation capacity and osteogenic differentiation potential CONCLUSIONS: AF-MSCs have a better performance in vivo bone healing than that of BM-MSCs. Hence, AF derived MSCs is highly recommended as an alternative source to BM-MSCs in bone regeneration and spine fusion surgeries. Moreover, the usage of gel-foam as a scaffold proved as an efficient cell carrier that showed bio-compatibility with cells, bio-degradability and osteoinductivity in vivo.