Cultivated murine bone marrow mesenchymal stem cells (MSCs) frequently accumulate chromosome abnormalities, become oncogenically transformed, and generate sarcomas when transplanted in mice. Although human MSCs appear to be more resistant, oncogenic transformation has also been observed in MSCs cultivated past the senescence phase. Cell therapy for tissue regeneration using human autologous MSCs requires transplantation of cells previously expanded in vitro. Thus, an important concern is to determine if oncogenic transformation is a necessary outcome of the expansion procedures. We have analyzed the proliferation capacity, organ colonization, and oncogenicity of enhanced green fluorescent protein and luciferase-labeled human adipose tissue-derived mesenchymal stem cells (hAMSCs), implanted in immunocompromised mice during a prolonged time period (8 months) using a non-invasive bioluminescence imaging procedure. Our data indicates that the liver was the preferred target organ for colonization by intramuscular or intravenous implantation of hAMSCs. The implanted cells tended to maintain a steady state, population did not proliferate rapidly after implantation, and no detectable chromosomal abnormalities nor tumors formed during the 8 months of residence in the host's tissues. It would appear that hAMSCs, contrary to their murine correlatives, could be safe candidates for autologous cell therapy procedures since in our experiments they show undetectable predisposition to oncogenic transformation after cultivation in vitro and implantation in mice.
Participation in clean-up of a major oil spill was associated with persistent respiratory symptoms, elevated markers of airway injury in breath condensate, and chromosomal damage.
The quantitative fluorescent PCR (QF-PCR) assay, introduced during the last few years, allows prenatal diagnoses of common chromosome aneuploidies in a few hours after sampling. We report the first assessment of QF-PCR performed on a large cohort of 18,000 consecutive clinical specimens analysed in two different Centres. All samples were analysed by QF-PCR using several selected STR markers together with amelogenin and, occasionally, SRY for fetal sexing. Results were compared with those obtained by conventional cytogenetic analysis. In 17,129 tests, normal fetuses were detected by QF-PCR. No false positives were observed. All 732 cases of trisomy 21, 18, 13, triploidies, double trisomies as well as all but one fetuses with X and Y aneuploidies were correctly diagnosed. Chromosome mosaicism could also be suspected in several samples. In some cases of in vitro culture failures, QF-PCR was the only evidence of fetal X, Y, 21, 18 and 13 chromosome complement. QF-PCR proved to be efficient and reliable in detecting major numerical chromosome disorders. The main advantages of the molecular assay are its very low cost, speed and automation enabling a single operator to perform up to 40 assays per day. QF-PCR relieves anxiety of most parents within 24 h from sampling and accelerates therapeutic interventions in the case of an abnormal result. In countries where large scale conventional cytogenetics is hampered by its high cost and lack of technical expertise, QF-PCR may be used as the only prenatal diagnostic test.
Our study supports the possibility of reducing the load of prenatal cytogenetic tests if the pregnancies are carefully monitored by non-invasive screening. In case of abnormal QF-PCR results, medical action can be taken within few hours from sampling. In cases of negative QF-PCR results, cytogenetic analyses might only be performed for fetuses with ultrasound abnormalities. In countries where large-scale cytogenetic tests are not available, QF-PCR may be used as the only prenatal diagnostic procedure.
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