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Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n=10), PMSC-ECM (42K cells/cm2) (n=8), PMSC-ECM (167K cells/cm2) (n=7), or PMSC-ECM (250–300K cells/cm2) (n=8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional area which were then normalized to normal lambs. Large neurons (LN, diameter 30–70μm) were counted manually and density calculated per mm2 gray matter. Results: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5–15]) than ECM alone (6.5 [IQR 4–12.75], p=0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167K/cm2) group (p=0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250–300K/cm2) group (p=0.045) which positively correlated with SLR score (r=0.807, p<0.0001). Conclusions: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function.

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In recent years, successful examples of antisense oligonucleotide (AS) therapy for genetic diseases have stimulated scientists to investigate its application on cancer diseases. AS can be used to down-regulate the mRNA and protein expression by annealing to specific region of the target mRNA which is responsible for the malignancy. Glucose transporter 5 (Glut5) is a tissue specific transporter that can be found on breast cancer tissues but not on normal breast tissues. Therefore, it is of clinical interest to investigate whether AS against Glut5 mRNA can tackle breast cancer. In this study, two cell lines, MCF-7 which is estrogen-receptor positive and MDA-MB-231 which is estrogen-receptor negative, were used to mimic breast cancer tissues at early and late stages, respectively. A 15-base sequence around the start codon of Glut5 was used. It was found that AS against Glut5 exerted anti-proliferative effect on both of these two breast tumor cell lines and seemed to exert its effect via the suppression of expression of Glut5 proteins in the cells. AS against Glut5 exhibited no effect on human hepatoma HepG2 cells which do not possess any Glut5. The results imply an alternative way in treating breast tumor as the AS against Glut5, unlike tamoxifen, takes effect on breast tumor cells via suppressing the expression of Glut5 that they specifically possess, and regardless whether the breast tumors are estrogen dependent or not.