The fate of heterotopically grafted neural precursor cells in the normal and dystrophic adult mouse retina

PURPOSE. To study the integration and differentiation of heterotopically transplanted neural precursor cells in the retina of adult mouse mutants displaying apoptotic degeneration of photoreceptor cells. METHODS. Neural precursor cells were isolated from the spinal cord of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein. Cells were expanded in vitro and transplanted into the retina of adult wild-type and age-matched ␤2/␤1 knock-in mice. ␤2/␤1 knock-in mutants display apoptotic death of photoreceptor cells and were generated by placing the cDNA of the ␤1 subunit into the gene of the ␤2 subunit of Na,K-ATPase. The integration and differentiation of grafted cells in recipient retinas was studied 1 or 6 months after transplantation. RESULTS. Mutant retinas contained more donor-derived cells than wild-type hosts. Moreover, in mutants, donor cells integrated into deeper retinal layers. In both genotypes, grafted cells differentiated into astrocytes and oligodendrocytes. Only a few ganglion cell axons were myelinated by donor-derived oligodendrocytes 1 month after transplantation, whereas extensive myelination of the nerve fiber layer was observed 6 months after transplantation. Unequivocal evidence for differentiation of grafted cells into neurons was not obtained. CONCLUSIONS. Heterotopically transplanted neural precursor cells are capable of integrating, surviving, and differentiating into neural cell types in normal and dystrophic retinas of adult mice. The particular environment of a pathologically altered retina facilitates integration of transplanted precursor cells. In principle, neural precursors may thus be useful to substitute for or replace dysfunctional or degenerated cell types. Results of the present study also indicate that replacement of retinal cell types is likely to require more appropriate donor cells, such as retinal precursor cells. (Invest Ophthalmol Vis Sci. 2001;42:3311-3319) I nherited retinal dystrophies are a heterogeneous group of disorders characterized by progressive retinal degeneration. Effective therapeutic treatments of retinal dystrophies in humans are currently not available. However, animal experiments have shown beneficial effects of various therapeutic strategies, including gene therapy to substitute for the pathogenic gene, application of growth factors to minimize cell degeneration, or transplantation of committed cell types to replace dysfunctional or degenerated cells. 10 -12 Neural precursors have been isolated from the developing and adult brain and can be massively expanded in vitro, providing, in principle, unlimited amounts of cell material for transplantation (different from primary retinal cells). When transplanted into the developing or adult brain, they have been demonstrated to integrate extensively into the recipient tissue, to survive for extended periods, and to eventually differentiate into those cell types that are affected in the host. 22 These cells were expanded in vitro in the presence of mitogens and subsequently transplanted into the retina of adult wild-type mice and mouse mutants displaying apoptotic degeneration of photoreceptor cells. As a mutant host, we used ␤2/␤1 knock-in mice. 23 ␤1 and ␤2 are subunits of Na,K-ATPase, a heterodimeric ion pump additionally consisting of a catalytic ␣-subunit. 23,24 ␤-subunits play a pivotal role for the formation of functional Na,K-ATPases as exemplified, for instance, by the severe phenotype of ␤2-deficient mice. 25 Such mice display a variety of severe defects in the central nervous system (CNS), including massive apoptotic degeneration of photoreceptor cells, and die at the end of the third postnatal week. 23 To obtain information about the fate of heterotopically transplanted neural precursor cells in the normal and dystrophic mouse retina, we isolated such cells from the spinal cord of EGFP transgenic mice and transplanted them into the retinas of adult wild-type mice and ␤2/␤1 knock-in mutants. Heterotopically transplanted neural precursor cells integrated into the mutant retina without disrupting the histoarchitecture of the host tissue. Quantitative investigations revealed that donorderived cells were more numerous and more widely distributed in mutant retinas than in retinas of age-matched wild-type From th

Radial head and neck fractures in children and adolescents

BackgroundRadial head and neck fractures are a rare entity in pediatric patients. Due to specific characteristics of the blood supply and remodeling potential, the correct diagnosis and initiation of appropriate therapy are crucial for the outcome. Therefore, the aim of this retrospective observational study was to present the outcome of a series of pediatric patients with radial head and neck fractures.MethodsIn total, 67 pediatric and adolescent patients with a fracture of the proximal radius admitted to a Level I Trauma Center (Germany) between 2005 and 2017 were included in this retrospective observational study. Patients were stratified in accordance with the classification of Judet modified by Metaizeau and with the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO-PCCF).ResultsAO-PCCF fracture type of proximal radius was age-dependent. Epiphyseal axis angle and displacement angle correlated significantly. Fractures treated with a K-wire or embrochage centromedullaire elastique stable (ECMES) presented higher displacement angles. The duration of callus formation was dependent on both the reduction technique and fracture displacement. The range of motion after complete fracture consolidation was dependent on the Metaizeau type and reduction technique but independent of the duration of immobilization and physical therapy.Conclusion and clinical relevanceBoth the epiphyseal axis and displacement angle are suitable for measuring the initial fracture displacement in radiographs. Consolidation is dependent on the initial displacement and reduction technique. The mini-open approach leads to a worse reduction result, later callus formation, and a more restricted range of motion in terms of pronation. Furthermore, the range of motion at follow-up is independent of the duration of immobilization and physiotherapy

Untersuchungen zur Pharmakokinetik der Salpetersaeureester trans-2-Amino-2-methyl-N-(4-nitroxycyclohexylmethyl)-propionsaeureamid (BM 12.1200) und 4-(2-Nitroxyethyl)-piperidin (BM 12.1173) sowie zur Biotransformation und Pharmakokinetik von trans-2-Amino-2-methyl-N-(4-nitroxycyclohexyl)-propionsaeureamid (BM 12.1179) im Hund

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