Experimental studyStem Cell Transplantation: The Lung Barrier
Section snippets
Cell Isolation and Labeling
MSCs were isolated from the long bones of Balb/c mice, purified, and characterized as CD34−, CD45− CD90+, CD44+, CD14−, c-kit−, sca-1+, and CD105+. Cells were made to express firefly luciferase under cytomegalovirus (CMV) promoter control by transfecting Phoenix cells with 10 μg of pRluc DNA9 as previously described10 and infecting wild-type MSC with the resultant viral supernatants. Stable transfectants were enriched by puromycin selection at 0.5 μg/mL, which was the concentration determined
Cell Injection
After administration of 0.5 × 106 MSCs, we noticed episodes of tachypnea, apnea, and hemodynamic alterations characteristic of pulmonary embolism in the group without SN pretreatment. These symptoms could be markedly reduced with prior vasodilator treatment.
In Vivo Imaging, Microsphere Trapping, and Histopathology
After MSC IV infusion without pretreatment, bioluminiscensce signals associated with MSCs were detected primarily in the lungs (Fig 1A). Ex vivo assessments of isolated organs confirmed high lung signals in contrast to only trace signals
Discussion
Using microspheres, we demonstrated that the mean size of suspended MSCs is larger than the size of pulmonary capillaries. Thus, because of their large size, major amounts of IV-injected MSCs are trapped within the pulmonary capillaries, causing pulmonary and hemodynamic alterations, and preventing the intended access to other organs. Because MSCs are naturally located within the bone marrow and are only occasionally liberated into the circulation, their size is usually not a barrier to their
Acknowledgment
S.S. and T.D. equally contributed to this work.
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Supported by a research grant from the Deutsche Forschungsgemeinschaft (DFG) (SCHR992/2-1) to S.S.