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

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

Correspondence and requests for reprints should be addressed to Carolyn Lutzko Ph.D., Children's Hospital Los Angeles, Division of Research Immunology and Bone Marrow Transplantation, 4650 Sunset Blvd., MS #62, Los Angeles, CA 90027. 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 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.

Key Words: extracorporeal membrane oxygenation • hematopoietic progenitors • mesenchymal progenitors • epithelial progenitors • circulating progenitors

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Studies have demonstrated graft-host chimerism in injured heart or lungs after hematopoietic stem cell or solid organ transplantation. The mechanism for the tissue chimerism is unknown. What This Study Adds to the Field Hematopoietic, mesenchymal, and epithelial progenitor populations can be identified in the blood of patients with acute severe cardiorespiratory failure who require extracorporeal membrane oxygenation (ECMO) support. Circulating hematopoietic progenitor frequency in patients undergoing ECMO was higher than in ICU control subjects. Circulating hematopoietic progenitor frequency in patients undergoing ECMO suggests that progenitor levels are increased in the setting of severe disease.