Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy.
ABSTRACT We investigated the kinetics of human mesenchymal stem cells (MSCs) after intravascular administration into SCID mouse cremaster vasculature by intravital microscopy. MSCs were injected into abdominal aorta through left femoral artery at two different concentrations (1 x 10(6) or 0.2 x 10(6) cell). Arterial blood velocity decrease by 60 and 18% 1 min after high/low dose MSCs injection respectively. The blood microcirculation was interrupted after 174+/-71 and 485+/-81 s. Intravital microscopy observation and histopathologic analysis of cremaster muscles indicated MSCs were entrapped in capillaries in both groups. 40 and 25% animals died of pulmonary embolism respectively in both high and low MSCs dose groups, which was detected by histopathologic analysis of the lungs. Intraarterial MSCs administration may lead to occlusion in the distal vasculature due to their relatively large cell size. Pulmonary sequestration may cause death in small laboratory animals. MSCs should be used cautiously for intravascular transplantation.
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ABSTRACT: The role of mesenchymal stem cells (MSCs) in cancer development is still controversial. MSCs may promote tumor progression through immune modulation, but other tumor suppressive effects of MSCs have also beendescribed. The discrepancy between these results may arise from issues related to different tissue sources, individual donor variability, and injection timing of MSCs. The expression of critical receptors such as Toll-like receptor is variable a teach time point of treatment, which may also determine the effects of MSCs on tumor progression. However, factors released from malignant cells, as well as surrounding tissues and the vasculature, are still regarded as a "black box. " Thus, it is still difficult to clarify the specific role of MSCs in cancer development. Whether MSCs support or suppress tumor progression is currently unclear, but it is clear that systemically administered MSCs can be recruited and migrate toward tumors. These findings are important because they can be used as a basis for initiating studies to explore the incorporation of engineered MSCs as novel anti-tumor carriers, for the development of tumor-targeted therapies.Frontiers in Genetics 11/2013; 4:261. DOI:10.3389/fgene.2013.00261
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ABSTRACT: Mesenchymal stem cells (MSCs) have shown extreme clinical promise as a therapeutic regenerative system in the treatment of numerous types of diseases. A recent report, however, documented lethal pulmonary thromboembolism in a patient following the administration of adipose-derived MSCs (ADSCs). In our study, we designed experiments to examine the role of tissue factor (TF), which is highly expressed at the level of mRNA and localized to the cell surface of cultured MSCs, as a triggering factor in the procoagulative cascade activated by infused MSCs. A high mortality rate of ∼85% in mice was documented following intravenous infusion of mouse ADSCs within 24 hours due to the observation of pulmonary embolism. Rotation thromboelastometry and plasma clotting assay demonstrated significant procoagulation by the cultured mouse ADSCs, and preconditioning of ADSCs with an anti-TF antibody or usage of factor VII deficient plasma in the assay successfully suppressed the procoagulant properties. These properties were also observed in human ADSCs, and could be suppressed by recombinant human thrombomodulin. In uncultured mouse adipose-derived cells (ADCs), the TF-triggered procoagulant activity was not observed and all mice infused with these uncultured ADCs survived after 24 hours. This clearly demonstrated that the process of culturing cells plays a critical role in sensitizing these cells as a procoagulator through the induction of TF expression. Our results would recommend that clinical applications of MSCs to inhibit TF activity using anti-coagulant agents or genetic approaches to maximize clinical benefit to the patients.Biochemical and Biophysical Research Communications 01/2013; 431(2). DOI:10.1016/j.bbrc.2012.12.134
- Tissue Regeneration - From Basic Biology to Clinical Application, 03/2012; , ISBN: 978-953-51-0387-5