title: Multicellular spheroids of bone marrow stromal cells: a three-dimensional in vitro culture system for the study of hematopoietic cell migration.
abstract: Cell fate decisions are governed by a complex interplay between cell-autonomous signals and stimuli from the surrounding tissue. In vivo cells are connected to their neighbors and to the extracellular matrix forming a complex three-dimensional (3-D) microenvironment that is not reproduced in conventional in vitro systems. A large body of evidence indicates that mechanical tension applied to the cytoskeleton controls cell proliferation, differentiation and migration, suggesting that 3-D in vitro culture systems that mimic the in vivo situation would reveal biological subtleties. In hematopoietic tissues, the microenvironment plays a crucial role in stem and progenitor cell survival, differentiation, proliferation, and migration. In adults, hematopoiesis takes place inside the bone marrow cavity where hematopoietic cells are intimately associated with a specialized three 3-D scaffold of stromal cell surfaces and extracellular matrix that comprise specific niches. The relationship between hematopoietic cells and their niches is highly dynamic. Under steady-state conditions, hematopoietic cells migrate within the marrow cavity and circulate in the bloodstream. The mechanisms underlying hematopoietic stem/progenitor cell homing and mobilization have been studied in animal models, since conventional two-dimensional (2-D) bone marrow cell cultures do not reproduce the complex 3-D environment. In this review, we will highlight some of the mechanisms controlling hematopoietic cell migration and 3-D culture systems.
authors.affiliation: Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. idrossi@hucff.ufrj.br
authors.forename: M I D
authors.initials: MI
authors.lastname: Rossi
authors.forename: A P D N
authors.initials: AP
authors.lastname: Barros
authors.forename: L S
authors.initials: LS
authors.lastname: Baptista
authors.forename: L R
authors.initials: LR
authors.lastname: Garzoni
authors.forename: M N
authors.initials: MN
authors.lastname: Meirelles
authors.forename: C M
authors.initials: CM
authors.lastname: Takiya
authors.forename: B M O
authors.initials: BM
authors.lastname: Pascarelli
authors.forename: H S
authors.initials: HS
authors.lastname: Dutra
authors.forename: R
authors.initials: R
authors.lastname: Borojevic
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D018929:Cell Culture Techniques / Q000379:methods*; D002465:Cell Movement / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D018874:Spheroids, Cellular / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology