Cultured human umbilical cord mesenchymal stem cells (hUC-MSCs) are being tested in several clinical trials and encouraging outcomes have been observed. To determine whether in vitro expansion influences the genomic stability of hUC-MSCs, we maintained nine hUC-MSC clones in long-term culture and comparatively analyzed them at early and late passages. All of the clones senesced in culture, exhibiting decreased telomerase activity and shortened telomeres. Two clones showed no DNA copy number variations (CNVs) at passage 30 (P30). Seven clones had ≥1 CNVs at P30 compared with P3, and one of these clones appeared trisomic chromosome 10 at the late passage. No tumor developed in immunodeficient mice injected with hUC-MSCs, regardless of whether the cells had CNVs at the late passage. mRNA-Seq analysis indicated that pathways of cell cycle control and DNA damage response were downregulated during in vitro culture in hUC-MSC clones that showed genomic instability, but the same pathways were upregulated in the clones with good genomic stability. These results demonstrated that hUC-MSCs can be cultured for many passages and attain a large number of cells, but most of the cultured hUC-MSCs develop genomic alterations. Although hUC-MSCs with genomic alterations do not undergo malignant transformation, periodic genomic monitoring and donor management focusing on genomic stability are recommended before these cells are used for clinical applications.
Recent observations of the light component of the cosmic-ray spectrum have revealed unexpected features that motivate further and more precise measurements up to the highest energies. The Dark Matter Particle Explorer (DAMPE) is a satellite-based cosmic-ray experiment that is operational since December 2015, continuously collecting data on high-energy cosmic particles with very good statistics, energy resolution, and particle identification capabilities. In this work, the latest measurements of the energy spectrum of proton+helium in the energy range from 46 GeV to 316 TeV are presented. Among the most distinctive features of the spectrum, a spectral hardening at ∼600 GeV has been observed, along with a softening at ∼29 TeV measured with a 6.6σ significance. Moreover, by measuring the energy spectrum up to 316 TeV, a strong link is established between space-and ground-based experiments, also suggesting the presence of a second hardening at ∼150 TeV. * https://geant4.web.cern.ch/node/302 † https://web.ikp.kit.edu/rulrich/crmc.html
OBJECTIVE: To investigate the effects of mandibular defects repaired by a tissue engineered bone complex with b-tricalcium phosphate (b-TCP) and bone morphogenic protein-2 (BMP-2) gene-modified bone marrow stromal cells (bMSCs). MATERIALS AND METHODS: bMSCs derived from Fisher 344 rats were cultured and transduced with adenovirus AdBMP-2, AdEGFP gene in vitro. Osteogenic differentiation of bMSCs was determined by alkaline phosphatase staining, von Kossa assay and reverse transcription-polymerase chain reaction. Gene transduced or untransduced bMSCs were seeded on b-TCP scaffolds to repair mandibular full thickness defects with a diameter of 5 mm. Eight weeks post-operation, X-ray examination, micro-computerized tomography and histological and histomorphological analysis were used to evaluate the bone healing effects. RESULTS: Alkaline phosphatase staining and mineralized nodules formation were more pronounced in AdBMP-2 group 14 days after gene transduction when compared with that of AdEGFP or untransduced group. The mRNA expression of osteopontin and osteocalcin also significantly increased 9 days after AdBMP-2 gene transduction. Mandibular defects were successfully repaired with AdBMP-2-transduced bMSCs ⁄ b-TCP constructs. The percentage of new bone formation in AdBMP-2 group was significantly higher than that of other control groups. CONCLUSIONS: Bone morphogenic protein-2 regional gene therapy together with b-TCP scaffold could be used to promote mandibular repairing and bone regeneration. Oral Diseases (2010) 16, 46-54
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