title: G-CSF-induced myeloid cells stimulated by TLR2 enhance engraftment after allogeneic hematopoietic stem cell transplantation.
abstract: A high frequency of G-CSF-mobilized myeloid cells (gMCs) in a donor graft accelerates hematopoietic recovery after peripheral blood stem cell transplantation (PBSCT). However, because of the limited functional efficacy of gMCs, repeated transfusions of gMCs are frequently required. In this study, we investigated a strategy to improve the functional capacity of gMCs during hematopoietic engraftment after allogeneic transplantation. We found that toll-like receptor 2 (TLR2) is constitutively expressed on gMCs. Treating gMCs with the synthetic TLR2 ligand Pam(3)CSK(4) (PAM) dramatically enhanced IL-10 and TNF-α production. However, PAM treatment does not induce substantial cellular maturation. Moreover, PAM treatment significantly improved gMC survival. PAM treated gMCs significantly promoted myeloid differentiation of donor hematopoietic stem cells (HSCs), resulting in accelerated engraftment after allogeneic transplantation. Our data suggest that TLR2-stimulated gMCs may be a novel cellular therapeutic for increasing the efficiency of allogeneic hematopoietic stem cell transplantation (HSCT) by reducing infectious complications associated with delayed engraftment.
authors.affiliation: Department of Hemato/Oncology, Busan Pak Hospital, College of Medicine, Inje University, Busan 614-735, Republic of Korea.
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Joo
authors.forename: Kyeong-Hee
authors.initials: KH
authors.lastname: Oh
authors.forename: Hae-Jeong
authors.initials: HJ
authors.lastname: Won
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Moon-Young
authors.initials: MY
authors.lastname: Choi
authors.forename: Gi-Ho
authors.initials: GH
authors.lastname: Han
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Inhack
authors.initials: I
authors.lastname: Choi
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D020869:Gene Expression Profiling; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D051195:Toll-Like Receptor 2; D016179:Granulocyte Colony-Stimulating Factor