title: Fetal liver stromal cells promote hematopoietic cell expansion.
abstract: Future application of hematopoietic stem and progenitor cells (HSPCs) in clinical therapies largely depends on their successful expansion in vitro. Fetal liver (FL) is a unique hematopoietic organ in which hematopoietic cells markedly expand in number, but the mechanisms involved remain unclear. Stromal cells (StroCs) have been suggested to provide a suitable cellular environment for in vitro expansion of HSPCs. In this study, murine StroCs derived from FL at E14.5, with a high level of Sonic hedgehog (Shh) and Wnt expression, were found to have an increased ability to support the proliferation of HSPCs. This effect was inhibited by blocking Shh signaling. Supplementation with soluble Shh-N promoted the proliferation of hematopoietic cells by activating Wnt signaling. Our findings suggest that FL-derived StroCs support proliferation of HSPCs via Shh inducing an autocrine Wnt signaling loop. The use of FL-derived StroCs and regulation of the Shh pathway might further enhance HPSC expansion.
authors.affiliation: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan, Hubei, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhou
authors.forename: Caihong
authors.initials: C
authors.lastname: Hu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Lifang
authors.initials: L
authors.lastname: Huang
authors.forename: Wenli
authors.initials: W
authors.lastname: Liu
authors.forename: Hanying
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology* / Q000502:physiology; D053823:Hedgehog Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D017154:Stromal Cells / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D051153:Wnt Proteins