Enduring allogeneic marrow engraftment via nonspecific bone- -marrow-derived regulating factors (mrf).

Abstract An ultrafiltration fraction of MW > 100,000 separated from the original medium in which bone marrow had been suspended (supernatant) stimulated incorporation of [ 3 H]thymidine by marrow in vitro and was designated marrow regulating factor (MRF). The administration of MRF to F 1 hybrid mice transplanted with parental bone marrow resulted in lasting chimerism of the surviving mice. A few of the hybrids receiving parental marrow but no MRF survived: however, none were chimeric. Administration of MRF after irradiation in C57BL/ 6 mice transplanted with bone marrow from DBA/2 and BALB/c donors resulted in endogenous reconstitution. However, administration of MRF before (preconditioning) and again after irradiation resulted in survival of the majority of mice. These C57BL/6 mice were chimeras of DBA/2 or BALB/c marrow but showed no sign of secondary disease. Thus the use of MRF abrogates resistance to and promotes engraftment of foreign marrow and enduring chimerism when the recipients (F 1 hybrids) appear to be nonreactive to the donor (parental marrow) and also when alloreactivity is bidirectional (allogeneic combinations).