Resolution and Relapse of Osteopetrosis in Mice Transplanted With Myeloid Tissue of Variable Histocompatibility

Osteopetrotic microphthalmic mice (mi/mi) were treated by injections of suspensions of myeloid tissue, newborns i.p., and weanlings i.v. Donated syngeneic material effected permanent cure of oteopetrosis provided that the dose was large enough (108 cells of bone marrow). H-2-compatible allogeneic bone marrow was initially as effective, but relapse ensued in immunocompetent mice. H-2-incompatible marrow was ineffective except in one set of newborn tolerant mice. Total body X-radiation in sublethal doses to recipients allowed permanent cure with H-2-compatible, and, in one circumstance, with H-2-incompatible marrow in smaller doses. The best results were obtained after lethal irradiation and the smaller dose of marrow. Results were checked by chromosome assay demonstrating that cure or relapse was correlated with permanent take or rejection, respectively, of a transplant in a recipient's bone marrow. Retention of donor lymphocytes alone was not associated with effective bony resorption; the candidate cell line for effectiveness remains the haematopoietic stem cell-monocyte-tissue phagocyte. Mammalian osteopetrosis is a disease characterised by deficient resorption of bone because of a failure of osteoclastic activity. This subject was recently reviewed by Marks and Walker (7). The injection of myeloid tissue from phenotypically normal donors resolves the osteopetrosis in microphthalmic mice which suffer from the disease (2, 3). Walker (2) reported that murine osteopetrosis based on a C57BL/6 background required lethal X-irradiation before cellular restoration, but in several Harwell stocks of newborn and weanling (17− to 22-day -old) microphthalmic mice, Loutit and Sansom (3) found that irradiation was unnecessary. Syngeneic and hemisyngeneic myeloid material was also effective in adult mice (4). This report confirms that maintained resolution depends on histo-compatibility of the donated material (5) and on the persistence of a detectable transplant in the bone marrow (6).