In vitro Paclitaxel and Radiation Effects on the Cell Types Responsible for Vascular Stenosis: A Preliminary Analysis

Zhang, J; Melhem, Murad; Kassing, W; Kelly, Burnett S.; Wang, Y; Krishnamoorthy, Mahesh; Heffelfinger, Sue C.; Desai, Pankaj B.; Roy‐Chaudhury, Prabir

doi:10.1159/000098018

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…Due to their sensitivity to PTX, ECs, as shown here and by other authors [16], can not be used for PTX loading. Other reports show that PTX is a strong inhibitor of fibroblasts and smooth muscle cell proliferation in vitro but do not investigate its toxicity [33], [34].…”

Section: Discussionmentioning

confidence: 98%

Mesenchymal Stromal Cells Primed with Paclitaxel Provide a New Approach for Cancer Therapy

et al. 2011

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BackgroundMesenchymal stromal cells may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that exposure of mouse bone marrow derived stromal cells to Doxorubicin led them to acquire anti-proliferative potential towards co-cultured haematopoietic stem cells (HSCs). We thus hypothesized whether freshly isolated human bone marrow Mesenchymal stem cells (hMSCs) and mature murine stromal cells (SR4987 line) primed in vitro with anti-cancer drugs and then localized near cancer cells, could inhibit proliferation.Methods and Principal FindingsPaclitaxel (PTX) was used to prime culture of hMSCs and SR4987. Incorporation of PTX into hMSCs was studied by using FICT-labelled-PTX and analyzed by FACS and confocal microscopy. Release of PTX in culture medium by PTX primed hMSCs (hMSCsPTX) was investigated by HPLC. Culture of Endothelial cells (ECs) and aorta ring assay were used to test the anti-angiogenic activity of hMSCsPTX and PTX primed SR4987(SR4987PTX), while anti-tumor activity was tested in vitro on the proliferation of different tumor cell lines and in vivo by co-transplanting hMSCsPTX and SR4987PTX with cancer cells in mice. Nevertheless, despite a loss of cells due to chemo-induced apoptosis, both hMSCs and SR4987 were able to rapidly incorporate PTX and could slowly release PTX in the culture medium in a time dependent manner. PTX primed cells acquired a potent anti-tumor and anti-angiogenic activity in vitro that was dose dependent, and demonstrable by using their conditioned medium or by co-culture assay. Finally, hMSCsPTX and SR4987PTX co-injected with human cancer cells (DU145 and U87MG) and mouse melanoma cells (B16) in immunodeficient and in syngenic mice significantly delayed tumor takes and reduced tumor growth.ConclusionsThese data demonstrate, for the first time, that without any genetic manipulation, mesenchymal stromal cells can uptake and subsequently slowly release PTX. This may lead to potential new tools to increase efficacy of cancer therapy.

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Section: Discussionmentioning

confidence: 98%

Mesenchymal Stromal Cells Primed with Paclitaxel Provide a New Approach for Cancer Therapy

et al. 2011

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“…The majority of isolated organisms from catheter-related bacteremia are gram-positive organisms (52-84%) with Staph Aureus responsible for the majority of these organisms 7,30,31,143,150,151 . Gram-negative are isolated in 27-36% of episodes and fungal isolated are relatively uncommon (<10%) [141][142][143]149,152 . Therefore, it is important to identify catheter-related bacteremia early so treatment can be initiated immediately.…”

Section: Catheter-related Bacteremiamentioning

confidence: 99%