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Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury

¹Will Rogers Institute Pulmonary Research Center, Division of Pulmonary and Critical Care Medicine, and ²Childrens Hospital Los Angeles, University of Southern California, Los Angeles, California

Submitted 4 June 2007 ; accepted in final form 23 May 2008

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/β₂ microglobulin (β₂M)^null mice were administered bleomycin (bleo) or saline intranasally. One, 2, 3 and 4 days after bleo or saline, human BMDC labeled with CellTracker Green CMFDA (5-chloromethylfluorescein diacetate) were infused intravenously. Retention of CMFDA⁺ cells was maximal when delivered 4 days after bleo treatment. Seven days after bleo, <0.005% of enzymatically dispersed lung cells from NOD/SCID mice were CMFDA⁺, which increased 10- to 100-fold in NOD/SCID/β₂M^null mice. Preincubation 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.

stromal-derived factor-1; CXCR4; CCXL12; homing; engraftment

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