Bone marrow mesenchymal stromal cells induce nitric oxide synthase-dependent differentiation of CD11b+cells that expedite hematopoietic recovery.
Bone marrow microenvironment is fundamental for hematopoietic homeostasis. Numerous efforts have been made to reproduce or manipulate its activity to facilitate engraftment after hematopoietic stem cell transplantation but clinical results remain unconvincing. This probably reflects the complexity of the hematopoietic niche. Recent data have demonstrated the fundamental role of stromal and myeloid cells in regulating hematopoietic stem cell self-renewal and mobilization in the bone marrow. In this study we unveil a novel interaction by which bone marrow mesenchymal stromal cells induce the rapid differentiation of CD11b+myeloid cells from bone marrow progenitors. Such an activity requires the expression of nitric oxide synthase-2. Importantly, the administration of these mesenchymal stromal cell-educated CD11b+cells accelerates hematopoietic reconstitution in bone marrow transplant recipients. We conclude that the liaison between mesenchymal stromal cells and myeloid cells is fundamental in hematopoietic homeostasis and suggests that it can be harnessed in clinical transplantation.
Division of Cancer Studies, King's College London, UK.
Cristina
C
Trento
Department of Haematology, Imperial College, London, UK.
Ilaria
I
Marigo
Division of Cancer Studies, King's College London, UK.|M.Tettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, Italy.
Alice
A
Pievani
Division of Cancer Studies, King's College London, UK.
Antonio
A
Galleu
Division of Cancer Studies, King's College London, UK.
Luigi
L
Dolcetti
Division of Cancer Studies, King's College London, UK.
Chun-Yin
CY
Wang
M.Tettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, Italy.
Marta
M
Serafini
Department of Medicine, Immunology Section, Verona University Hospital, Italy.
Vincenzo
V
Bronte
Division of Cancer Studies, King's College London, UK francesco.dazzi@kcl.ac.uk.|Department of Haematology, Imperial College, London, UK.
Francesco
F
Dazzi
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006706:Homeostasis; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*
D039481:CD11b Antigen; D052247:Nitric Oxide Synthase Type II