Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.

Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.

Phase relations of the olivine‐wadsleyite transition in the system (Mg,Fe)2SiO4 have been determined at 1600 and 1900 K using the quench method in a Kawai‐type high‐pressure apparatus. Pressure was determined at a precision better than 0.2 GPa using in situ X‐ray diffraction with MgO as a pressure standard. The transition pressures of the end‐member Mg2SiO4 are estimated to be 14.2 and 15.4 GPa at 1600 and 1900 K, respectively. Partition coefficients for Fe and Mg between olivine and wadsleyite are 0.51 at 1600 K and 0.61 at 1900 K. By comparing the depth of the discontinuity with the transition pressure, the temperature at 410 km depth is estimated to be 1760 ± 45 K for a pyrolitic upper mantle. The mantle potential temperature is estimated to be in the range 1550–1650 K. The temperature at the bottom of the upper mantle is estimated to be 1880 ± 50 K. The thickness of the olivine‐wadsleyite transition in a pyrolitic mantle is determined to be between 7 and 13 km for a pyrolitic mantle, depending on the efficiency of vertical heat transfer. Regions of rapid vertical flow (e.g., convection limbs), in which thermal diffusion is negligible, should have a larger transition interval than stagnant regions, where thermal diffusion is effective. This is in apparent contradiction to short‐period seismic wave observations that indicate a maximum thickness of <5 km. An upper mantle in the region of the 410 km discontinuity with about 40% olivine and an Mg# of at least 89 can possibly explain both the transition thickness and velocity perturbation at the 410 km discontinuity.

No abstract