Submitted on June 4, 2007
Accepted on May 23, 2008
RETENTION OF HUMAN BONE MARROW-DERIVED CELLS IN MURINE LUNGS FOLLOWING BLEOMYCIN-INDUCED LUNG INJURY
Janice Marie Liebler1*, Carolyn Lutzko2, Agnes Banfalvi1, Dinithi Senadheera2, Neema Aghamohammadi1, Edward D. Crandall1, and Zea Borok1
1 Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, California, United States
2 Childrens Hospital Los Angeles, University of Southern California, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: liebler{at}usc.edu.
We studied the capacity of adult human bone marrow-derived cells (BMDC) to incorporate into distal lung of immunodeficient mice following lung injury. Immunodeficient NOD/SCID and NOD/SCID/
2 microglobulin (2M)null mice were administered bleomycin (bleo) or saline intranasally. 1, 2, 3 and 4 days after bleo or saline, human BMDC labeled with CellTrackerTM Green CMFDA (5-chloromethylfluorescein diacetate) were infused intravenously. Retention of CMFDA+ cells was maximal when delivered 4 days after bleo treatment. 7 days after bleo, <0.005% of enzymatically dispersed lung cells from NOD/SCID mice were CMFDA+, which increased 10-100 fold in NOD/SCID/2Mnull mice. Pre-incubation of BMDC with Diprotin A, a reversible inhibitor of CD26 peptidase activity that enhances the Stromal-derived factor-1 (SDF-1/CXCL12)/CXCR4 axis, resulted in a 30% increase in the percentage of CMFDA+ cells retained in the lung. These data indicate that human BMDC can be identified in lungs of mice following injury, albeit at low levels, and this may be modestly enhanced by manipulation of the SDF-1/CXCR4 axis. Given the overall low number of human cells detected, methods to increase homing and retention of adult BMDC, and consideration of other stem cell populations, will likely be required to facilitate engraftment in the treatment of lung injury.
