Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury.
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/beta(2) microglobulin (beta(2)M)(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/beta(2)M(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.
Liebler
Janice M
JM
Will Rogers Institute Pulmonary Research Center, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, California 90033, USA. liebler@usc.edu
Lutzko
Carolyn
C
Banfalvi
Agnes
A
Senadheera
Dinithi
D
Aghamohammadi
Neema
N
Crandall
Edward D
ED
Borok
Zea
Z
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D055370:Lung Injury; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009842:Oligopeptides / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D014183:Transplantation, Heterologous
D000903:Antibiotics, Antineoplastic; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009842:Oligopeptides; D019718:Receptors, CXCR4; D001761:Bleomycin; C041445:diprotin A; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4