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  • 1
    Keywords: CELLS ; EXPRESSION ; IN-VITRO ; proliferation ; tumor ; IN-VIVO ; MODEL ; THERAPY ; DISEASE ; DISEASES ; GENE ; MICE ; TRANSPLANTATION ; BONE-MARROW ; NOD/Scid mice ; MOUSE ; MOUSE MODEL ; cord blood ; ONCOLOGY ; interaction ; BLOOD PROGENITOR CELLS ; SDF-1 ; FATE ; REPOPULATION ; mesenchymal stromal cells ; ENGRAFTMENT ; NOD/SCID/B2M(NULL) MICE
    Abstract: Abstract Background aims. Transplantation of allogeneic hematopoietic stem cells (HSC) within the framework of hematologic oncology or inherited diseases may be associated with complications such as engraftment failure and long-term pancytopenia. HSC engraftment can be improved, for example by co-transplantation with mesenchymal stem cells (MSC). Recently, a new multipotent MSC line from umbilical cord blood, unrestricted somatic stem cells (USSC), has been described. It was demonstrated that USSC significantly support proliferation of HSC in an in vitro feeder layer assay. Methods. A NOD/SCID mouse model was used to assess the effect of USSC on co-transplanted CD34(+) cells and look for the fate of transplanted USSC. The migration potential of USSC was studied in a Boyden chamber migration assay and in vivo. Quantitative real-time polymerase chain reaction (qRT-PCR) for CXCR4, CD44, LFA1, CD62L, VLA4, RAC2, VLA5A and RAC1 were performed. NMR1 nu/nu mice were used for a tumorigenicity test. Results. After 4 weeks, homing of human cells (CD45(+)) to the bone marrow of NOD/SCID mice was significantly increased in mice co-transplanted with CD34(+) cells and USSC (median 30.9%, range 7-50%) compared with the CD34(+) cell-only control group (median 5.9%, range 3-10%; P = 0.004). Homing of USSC could not be shown in the bone marrow. A cell-cell contact was not required for the graft enhancing effect of USSC. An in vivo tumorigenicity assay showed no tumorigenic potential of USSC. Conclusions. This pre-clinical study clearly shows that USSC have an enhancing effect on engraftment of human CD34(+) cells. USSC are a safe graft adjunct.
    Type of Publication: Journal article published
    PubMed ID: 20950214
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  • 2
    ISSN: 1432-1238
    Keywords: Selective decontamination of the digestive tract (SDD) ; Intensive care unit (ICU) ; Bacterial colonization ; Tracheobronchial aspirates ; Antibiotic resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To evaluate the effect of the prolonged systematic use of topical SDD (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on ICU ecology as expressed by changes in tracheal colonization and bacterial resistances. Design Prospective microbiological survey. Setting Polyvalent ICU of a 2000 beds general hospital. Patients Data concerning bacterial strains isolated from the tracheo-bronchial aspirates of all the patients admitted to a polyvalent ICU over 3 consecutive periods of 12 months ('88, '89, '90) were prospectively entered in a database and subsequently analyzed. During a 3-year period 502 patients required artificial ventilation for more than 72 h and 332 of them ('89 and '90) were treated with SDD. All samples collected within 72 h from ICU admission were excluded as well as duplicate samples from the same patients. Intervention All the patients admitted to the ICU in '89 and '90 and submitted to artificial ventilation for at least 24 h were routinely treated with topical SDD without i.v. antibiotic prophylaxis; in '88 SDD was not empoloyed. Measurements and results Criteria for collecting sputum samples and microbiological procedures remained unchanged troughout the study-time. Positive sputum were significantly less in '89 (80.8% versus 92.3%p〈0.001) and this was due to a very sharp decrease in the isolation of Gram-negative strains from 43–28% (−64%p〈0.0001) involving both:Enterobacteriaceae (−45%) andPseudomonaceae (−77%). In 1990; however, a new increase in Gram negative was observed, although the overall amount of Gram-negative was still 49% lower in '90 if compared to '88 (p〈0.0001). A dramatic increase inPseudomonas isolation was the only factor responsible for the “rebound” observed. An increasing percentage ofPseudomonas developed a resistance towards tobramycin and only 45% ofPseudomonas strains turned out to be sensible to tobramycin in '90 against 79% in '88. A similar trend was registered for all aminoglycosides with the exception of amikacin. Gram-positive colonizations tended to increase (+63%) (p〈0.0001) and this was mainly due to Coagulase negativeStaphylococci (+290%p〈0.0001) andS. pneumoniae, whereasS. aureus isolations decreased (−18%) but not significantly. Conclusions Our data suggest that the prolonged use of SDD is associated with dramatic changes in ICU ecology: the incidence of Gram negative colonization is significantly diminished by SDD whereas Gram positive tend to increase.Pseudomonas developed an increasing resistance towards tobramycin one of the components of the SDD formula we used.
    Type of Medium: Electronic Resource
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