THE ROLE OF SHEEP STROMA IN HUMAN HEMATOPOIESIS IN THE HUMAN SHEEP CHIMERAS/

We have previously reported on the successful engraftment and long-ter m expression of human HSC (haemopoietic stem cells) in sheep following transplantation into pre-immune fetuses. The mechanism(s) underlying the support/maintenance of human haemopoiesis in sheep is not understo od. In these studies we examined the ability of sheep stroma to suppor t human haemopoiesis in vitro and compared this with support provided by human stroma. We found that, overall, human stroma was significantl y more effective than sheep stroma in supporting human haemopoiesis in vitro. Nevertheless, stroma established from bone marrow of normal sh eep was capable of lower-level support of the proliferation and multil ineage differentiation of highly purified (CD34(+), CD38(-)) preparati ons of human HSC in vitro. At lower concentrations, sheep stroma condi tioned media (CM) induced human bone marrow mononuclear cells enriched for the CD34-positive fraction to enter the cell cycle at levels comp arable to that of human stroma CM. However, unlike human CM, at higher concentrations, sheep CM inhibited human cells from initiating the ce ll cycle. These results provide a possible explanation for the longter m maintenance of low levels of human haemopoietic cell activity in hum an/sheep chimaeras.