Induction of hematopoietic microenvironment by the extracellular matrix from long-term bone marrow cultures

Extracellular matrix (ECM) plays an important role in the regulation of hematopoiesis. The ECM obtained from murine long-term bone marrow cultures (LTBMCs) induces hematopoietic foci formation within 3 months after implantation under the murine renal capsule. The foci consist of approximately 3 x 10(6) hematopoietic cells and function for at least 11 months. The induced stroma contains transplantable precursors capable of transferring a hematopoietic microenvironment to secondary recipients, and is insensitive to the stroma-stimulating factor produced in recipient mice after irradiation. The ECM induces hematopoietic foci formation in chimeras irradiated by a dose which is lethal for most of the stromal precursors. These facts point to the differences observed between bone marrow stromal precursors and mesenchymal cells induced under the renal capsule. The foci contain bone, but its appearance is limited to early stages of foci growth, and depends on the dose of implanted ECM. Bone is not formed when the xenogeneic ECM from nonhematopoietic tissue is used as an inducer. In this case, the foci develop slowly and are observed only to the tenth month after implantation. The data obtained demonstrate a novel function of the ECM in the induction of a hematopoietic microenvironment.