By deriving mast cells in vitro from genetically manipulated embryonic stem cells, a team of researchers have overcome the problem of analyzing embryonic lethal mutations. The work also paves the way for tissue engineering, in which highly differentiated cell types could be generated in vitro and transplanted to restore specific functions in vivo. Previously, mast cells were shown to be generated from hematopoietic precursors in vitro, making mast cells an attractive target for the new work, which is described in a recent issue of PNAS (97, 9186–9190, 2000). The researchers generated mast cells from both wild-type embryonic stem cells and stem cells carrying a homozygous deletion of SEK1. Although SEK1 has been implicated in certain mast cell activities, the knockout has been difficult to study because of its embryonic lethal phenotype. The team found that both wild-type and SEK1 knockout mast cells appear to function normally after transplantation into a mast cell–deficient mouse strain. Stephen Galli, a researcher at the Stanford University School of Medicine (Stanford, CA) and senior author on the study, explains that the new approach has broad potential, because “mast cells are thought to participate importantly in many biological responses … such as angiogenesis, wound healing and tissue remodeling, responses to neoplasms, and non-immunological forms of chronic inflammation, to name just a few.”