RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 INDUCES A HEMATOPOIETIC MICROENVIRONMENT IN THE RAT THAT SUPPORTS THE GROWTH OF STEM-CELLS

In the mammalian bone marrow, stromal components support the growth an d differentiation of blood cells. To study this complex system, we use d a rat model in which ectopic hematopoietic tissue was induced to for m after subcutaneous implantation of recombinant human bone morphogene tic protein (rhBMP-2). We showed that this organoid contained clonogen ic precursors of both erythroid and myeloid lineages and progenitors c ompetent to regenerate splenic lymphopoiesis. Furthermore, stem cells derived from ectopic foci conferred both short-term (30-day) and long- term (>6-month) protection in vivo against radiation-induced marrow ap lasia. Lead shielding of the ectopic marrow in situ also permitted end ogenous recovery of hematopoiesis after sublethal irradiation. Ex-tend ing previous observations that most fibroblastoid cells of the man ow stain with the anti-ST3 antibody (but minimally with anti-ST4), wherea s those growing from nonhematopoietic tissues react with anti-ST4, we found that analogous cells of the ectopic foci stained predominantly w ith anti-ST3. The ability to induce formation of a hematopoietic micro environment from mesenchymal precursors may make possible the developm ent of new strategies for the treatment of primary disorders of stem c ells and in irreversible stromal injury.