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Published ahead of print on October 29, 2009
Am. J. Respir. Crit. Care Med. 2009, doi:10.1164/rccm.200812-1901OC
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Submitted on December 16, 2008
Accepted on October 28, 2009

Recovery of Multipotent Progenitors from the Peripheral Blood of Patients Requiring ECMO Support

Kim Chi T Bui1, Dinithi Senadheera2, Xingchao Wang2, Benjamin Hendrickson3, Philippe Friedlich4, and Carolyn Lutzko2*

1 Mattel Children's Hospital at UCLA Medical Center, David Geffen School of Medicine, Los Angeles, California, United States, 2 Saban Research Institute at Childrens Hospital Los Angeles, Los Angeles, California, United States; Department of Pediatrics, Divsion of Research Immunology & Bone Marrow Transplantation, Childrens Hospital Los Angeles, Keck School of Medicine at the University of Southern California, Los Angeles, California, United States, 3 Department of Pediatrics, Divsion of Research Immunology & Bone Marrow Transplantation, Childrens Hospital Los Angeles, Keck School of Medicine at the University of Southern California, Los Angeles, California, United States, 4 Department of Pediatrics, Division of Neonatal Medicine, Childrens Hospital Los Angeles, Keck School of Medicine at the University of Southern California, Los Angeles, California, United States

* To whom correspondence should be addressed. E-mail: clutzko{at}chla.usc.edu.

Rationale: Studies have demonstrated that bone marrow derived cells can be recruited to injured lungs through an unknown mechanism. We hypothesize that marrow progenitors are mobilized into the circulation of patients with cardiac and/or respiratory failure, and may then traffic to, and incorporate into the sites of tissue injury. Objectives: To determine whether progenitor populations are increased in the blood of patients with severe acute cardio-respiratory failure placed on Extracorporeal Membrane Oxygenation (ECMO). Methods: Mononuclear cells from ECMO, umbilical cord and control blood samples were evaluated in colony forming assays for hematopoietic, mesenchymal and epithelial cells. Progenitors were identified by proliferative and differentiative capacities, and confirmed by the expression of lineage specific markers. Main results: Significantly higher levels of hematopoietic progenitors were observed in ECMO (n=41) samples than NICU (n=16) or PICU controls (n=14). Hematopoietic progenitor mobilization increased with time on ECMO support. Mesenchymal progenitors (MSC) were recovered from 18/58 ECMO samples with rapid sample processing (<4 hours) critical to their recovery. MSC were not recovered from normal controls. ECMO-derived MSC had osteogenic, chondrogenic and adipogenic differentiation potential. The recovery of MSC did not influence survival outcome (61%). Epithelial progenitors were observed in 8 ECMO samples but not in control samples. Their presence was associated with a lower survival trend (38%). Conclusions: Hematopoietic, mesenchymal and epithelial progenitors were mobilized into the circulation of patients on ECMO. This may reflect a response to severe cardiopulmonary injury, blood-foreign surface interactions with the ECMO circuit and/or hemodilution.


Key words: ECMO • epithelial progenitors • hematopoietic progenitors • mesenchymal progenitors • MSC







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