CD14+ cells from peripheral blood positively regulate hematopoietic stem and progenitor cell survival resulting in increased erythroid yield
Esther Heideveld,
Francesca Masiello,
Manuela Marra,
Fatemehsadat Esteghamat,
Nurcan Yağcı,
Marieke von Lindern,
Anna Rita F. Migliaccio,
Emile van den Akker
Affiliations
Esther Heideveld
Sanquin Research, Dept. of Hematopoiesis, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands
Francesca Masiello
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy
Manuela Marra
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy
Fatemehsadat Esteghamat
Sanquin Research, Dept. of Hematopoiesis, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands
Nurcan Yağcı
Sanquin Research, Dept. of Hematopoiesis, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands
Marieke von Lindern
Sanquin Research, Dept. of Hematopoiesis, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands
Anna Rita F. Migliaccio
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy;Division of Hematology and Medical Oncology, Mount Sinai School of Medicine and the Myeloproliferative Disorders Research Consortium, New York, NY, USA
Emile van den Akker
Sanquin Research, Dept. of Hematopoiesis, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands
Expansion of erythroblasts from human peripheral blood mononuclear cells is 4- to 15-fold more efficient than that of CD34+ cells purified from peripheral blood mononuclear cells. In addition, purified CD34+ and CD34− populations from blood do not reconstitute this erythroid yield, suggesting a role for feeder cells present in blood mononuclear cells that increase hematopoietic output. Immunodepleting peripheral blood mononuclear cells for CD14+ cells reduced hematopoietic stem and progenitor cell expansion. Conversely, the yield was increased upon co-culture of CD34+ cells with CD14+ cells (full contact or transwell assays) or CD34+ cells re-constituted in conditioned medium from CD14+ cells. In particular, CD14++CD16+ intermediate monocytes/macrophages enhanced erythroblast outgrowth from CD34+ cells. No effect of CD14+ cells on erythroblasts themselves was observed. However, 2 days of co-culturing CD34+ and CD14+ cells increased CD34+ cell numbers and colony-forming units 5-fold. Proliferation assays suggested that CD14+ cells sustain CD34+ cell survival but not proliferation. These data identify previously unrecognized erythroid and non-erythroid CD34− and CD34+ populations in blood that contribute to the erythroid yield. A flow cytometry panel containing CD34/CD36 can be used to follow specific stages during CD34+ differentiation to erythroblasts. We have shown modulation of hematopoietic stem and progenitor cell survival by CD14+ cells present in peripheral blood mononuclear cells which can also be found near specific hematopoietic niches in the bone marrow.
