ALL STEM CELLS

Stem Cell Transplantation: The Lung Barrier

http://www.ncbi.nlm.nih.gov/pubmed/17362785

ABSTRACT
Background. Mesenchymal stem cells (MSCs) show differentiation capacity along
mesenchymal lineages and have the potential to aid tissue regeneration. MSC transplantation
strategies are therefore currently being assessed following injury to various organs.
However, potential MSC migration to these organs after intravenous (IV) MSC injection
continues to be impeded by cell trapping within the lung.
Methods. Mouse MSCs were isolated, purified, transfected with firefly luciferase, and
labeled with CSFE. Their size was assessed in vitro. To estimate the diameter of mouse
pulmonary capillaries, fluorescence-labeled microspheres of different sizes were injected
with or without sodium nitroprusside (SN) pretreatment. The lungs were harvested after
30 seconds and mean numbers of trapped microspheres per high-power field (HPF) were
calculated. After IV injection of MSC suspensions (with or without SN), their dynamic
distribution was monitored by in vivo luciferine imaging as well as by histopathology.
Results. The diameter of suspended MSCs in vitro was 15 to 19 m. Whereas nearly no
4-m microspheres could be detected in lung sections, the numbers of trapped 10- and
15-m microspheres could be significantly decreased by prior SN injection from 19.3
11.1 to 6.0 1.6 cells/HPF (P .004) and from 34.9 11.9 to 25.6 8.1 cells/HPF (P
.028), respectively. Within seconds after MSC IV injection, the vast majority of cells was
found in the lungs. However, cell trapping in the pulmonary microvasculature was
significantly reduced by pre-treatment with SN.
Conclusions. We demonstrate that cell trapping in lungs can be reduced with IV SN
pretreatment, increasing MSC passage through the lung capillaries, and potentially
facilitating cell access to injured organs.



http://www.ncbi.nlm.nih.gov/pubmed/17362785