Recovery of Multipotent Progenitors from the Peripheral Blood of Patients Requiring Extracorporeal Membrane Oxygenation Support

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 cardiorespiratory 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. Measurements and Main Results: Significantly higher levels of hematopoietic progenitors were observed in ECMO (n = 41) samples than neonatal intensive care unit (n = 16) or pediatric intensive care unit 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 h) 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 eight 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.