Our previous study indicated that electroacupuncture (EA) could increase neurotrophin-3 (NT-3) levels in the injured spinal cord, stimulate the differentiation of transplanted bone marrow mesenchymal stem cells (MSCs), and improve functional recovery in the injured spinal cord of rats. However, the number of neuron-like cells derived from the MSCs is limited. It is known that NT-3 promotes the survival and differentiation of neurons by preferentially binding to its receptor TrkC. In this study, we attempted to transplant TrkC gene-modified MSCs (TrkC-MSCs) into the spinal cord with transection to investigate whether EA treatment could promote NT-3 secretion in the injured spinal cord and to determine whether increased NT-3 could further enhance transplanted MSCs overexpressing TrkC to differentiate into neuron-like cells, resulting in increased axonal regeneration and functional improvement in the injured spinal cord. Our results showed that EA increased NT-3 levels; furthermore, it promoted neuron-phenotype differentiation, synaptogenesis, and myelin formation of transplanted TrkC-MSCs. In addition, TrkC-MSC transplantation combined with EA (the TrkC-MSCs + EA group) treatment promoted the growth of the descending BDA-labeled corticospinal tracts (CSTs) and 5-HT-positive axonal regeneration across the lesion site into the caudal cord. In addition, the conduction of cortical motorevoked potentials (MEPs) and hindlimb locomotor function increased as compared to controls (treated with the LacZ-MSCs, TrkC-MSCs, and LacZ-MSCs + EA groups). In the TrkC-MSCs + EA group, the injured spinal cord also showed upregulated expression of the proneurogenic factors laminin and GAP-43 and downregulated GFAP and chondroitin sulfate proteoglycans (CSPGs), major inhibitors of axonal growth. Together, our data suggest that TrkC-MSC transplantation combined with EA treatment spinal cord injury not only increased MSC survival and differentiation into neuron-like cells but also promoted CST regeneration across injured sites to the caudal cord and functional improvement, perhaps due to increase of NT-3 levels, upregulation of laminin and GAP-43, and downregulation of GFAP and CSPG proteins.

CD271 has been applied to isolate mesenchymal stem cells (MSCs) from bone marrow and other tissues. Umbilical cord blood is a unique resource of stem cells and endothelial progenitor cells. Isolation of MSCs from umbilical cord blood, however, has been inefficient and inconsistent. This study was designed to examine the potential application of CD271 as a marker for the isolation of MSCs from umbilical cord blood. CD271+ cells were isolated from umbilical cord blood and bone marrow using CD271 antibody-conjugated microbeads, and characterized in osteogenic, chondrogenic and adipogenic differentiation. CD271+ cells from umbilical cord blood were slow to proliferate compared with those isolated from bone marrow. While CD271+ cells from bone marrow differentiated into osteogenic, chondrogenic and adipogenic lineages, there were no sound indications of differentiation by CD271+ cells from umbilical cord blood under the same differentiation conditions applied to the CD271+ cells from bone marrow. The study also found that bone marrow CD271+ cells remarkably upregulated the expression of chondrogenic genes under chondrogenic differentiation induction. When implanted into bone defects in mice, CD271+ cells from bone marrow regenerated significant bone, but the counterparts in umbilical cord blood formed little bone in the bone defects. In conclusion, CD271 is an efficient marker for MSC isolation from bone marrow but has failed to isolate MSCs from umbilical cord blood. CD271+ cells in bone marrow are particularly chondrogenic. The property of CD271+ cells is unique but varies from different tissues.

No abstract

Background: Human mesenchymal stem cells (MSCs) have been studied and applied extensively because of their ability to self-renew and differentiate into various cell types. Since most human diseases models are murine, mouse MSCs should have been studied in detail. The mdx mouse -a Duchenne muscular dystrophy model -was produced by introducing a point mutation in the dystrophin gene. To understand the role of dystrophin in MSCs, we compared MSCs from mdx and C57BL/10 mice, focusing particularly on the aspects of light and electron microscopic morphology, immunophenotyping, and differentiation potential.

The phosphatase FIG4 regulates the concentration of phosphatidylinositol 3,5-diphosphate (PI3,5P2), a molecule critical for endosomal/lysosomal membrane trafficking and neuron function. We investigated Fig4 expression in the developing CNS of mice and rats using Western blot, real-time polymerase chain reaction, and morphological techniques in situ and in vitro and after spinal cord injury. Fig4 was expressed at a high levels throughout development in myelinating cells, particularly Schwann cells, and dorsal root ganglia sensory neurons. Fig4 protein and mRNA in CNS neurons were markedly diminished in adult versus embryonal animals. Spinal cord hemisection induced upregulation of Fig4 in adult spinal cord tissues that was associated with accumulation of lysosomes in neurons and glia. This accumulation appeared similar to the abnormal lysosomal storage observed in dorsal root ganglia of young fig4-null mice. The results suggest that Fig4 is involved in normal neural development and the maintenance of peripheral nervous system myelin. We speculate that adequate levels of Fig4 may be required to prevent neurons and glia from excessive lysosomal accumulation after injury and in neurodegeneration.