Host origin of marrow stromal cells following allogeneic bone marrow transplantation

Abstract

Although it is generally agreed that stromal cells are important in the regulation of haematopoietic cell development^1–3, the origin of these phenotypically diverse cells has been a subject for debate for more than 50 years⁴. Data which support the concept of a separate origin for the haematopoietic stem cell and the marrow stroma are derived from cytogenetic or enzyme marker studies of explanted and expanded stromal cells grown under conditions that do not allow haematopoiesis in vitro^5–7. Recent evidence in man⁸ and in mouse⁹ suggesting that the stromal cells capable of transferring the haematopoietic microenvironment in vitro are trans-plantable seemingly questions this dichotomy, one interpretation being the existence of a common haematopoietic/stromal 'stem cell'. We used in situ hybridization to discriminate donor cells from host in blood and bone marrow samples obtained from patients with functioning sex-mismatched but HLA-identical allografts. Without exception, marrow-derived stromal cells that proliferate in long-term cultures were found to be of host genotype, whereas the macrophage component of the adherent layer in these cultures originated from the donor.