Molecular basis of homing of intravenously transplanted stem cells to the marrow.

OMING OF hematopoietic progenitors can be defined H as the set of molecular interactions that mediates the recognition of hematopoietic stem cells and other progenitor cells by marrow stroma after the progenitor cells are intravenously introduced into a recipient. Through this recognition mechanism, circulating progenitor cells bind selectively to the marrow stroma and begin the process of proliferation and differentiation. It is owing to the homing mechanism that bone marrow transplantation can be carried out by simple intravenous infusion of marrow rather than requiring a surgical operation, as is the case with the transplantation of other organs such as kidney, heart, or liver. Homing is mediated by membrane interactions between progenitor cells and stromal cells. A homing molecule on the surface of progenitor cells recognizes and binds to a corresponding molecule on the surface of stromal cells. With maturation, the progenitor cell may stop the synthesis and, consequently, can lose its homing molecule, which may be diluted as a result of frequent cell divisions without being replaced. Mature cells, therefore, do not possess the homing molecules7 and can be released into the circulation. Investigation into the molecular mechanism of homing was precluded by the lack of necessary molecular probes that would permit exploration of the specificity of this interaction. Because the nature of interaction was unknown, investigators did not know where to start to unveil the phenomenon. There was no direction to the field. The development of appropriate probes during the past decade has permitted certain information into the molecular nature of this interaction. Early evidence, derived from studies with lectin mitogen^,^*^**-'^ suggested that the molecular basis of recognition and homing may involve an interaction between a membrane lectin and appropriate configuration of certain carbohydrate groups of a membrane glycoconjugate, leading to the selective seeding of stem cells to the marrow. This suggestion gave a direction to the research in this area and led to the development and synthesis of a number of probes that facilitated the identification of the homing molecule. Parallel work on the traffic of lymphocytes indicated that a similar mechanism may also be involved in regulating the selective entry of lymphocytes into certain lymphoid organs"-" and, probably, the regulated delivery of mature blood cells from marrow into the circulation. '*20-27 This article is a critical review of information that has emerged concerning the homing of hematopoietic progenitor cells. Molecular mechanisms regulating the traffic of lymphocytes will also be briefly discussed.