Cellular specificity of the cure for osteopetrosis: isolation of and treatment with pluripotent hemopoietic stem cells.
Osteopetrosis in the ia rat is the result of reduced bone resorption due to abnormal osteoclasts. Studies in the ia mutant have shown that mononuclear cells from normal littermates could cure the skeletal sclerosis and result in the formation of normal osteoclasts when transplanted into ia rats. Recent studies demonstrated that the Ficoll-Hypaque isolates of spleen, bone marrow, and newborn liver were effective in curing the skeletal disease. These results suggest that the cellular source of the cure is a pluripotent hemopoietic stem cell (PHSC). Goldschneider et al. (1980) demonstrated that stem cells from rat bone marrow relatively large mononuclear cells that are strongly positive for Thy 1.1 antigen. Splenic and bone marrow samples from normal rats were treated with a monoclonal antibody developed against the rat Thy 1.1 antigen and guinea pig complement. This procedure was cytotoxic for 47% of the mononuclear spleen cells and 74% of the mononuclear bone marrow cells. When the Thy 1.1 depleted samples were transplanted into ia littermates, they were ineffective in reversing the osteoclast and bone resorption defects. Using the parameters described by Goldschneider, and fluorescence-activated cell sorting (FACS), the PHSC were isolated from normal rat bone marrow. The isolated cells were assayed for colony forming units--spleen (CFU-S) and were found to contain approximately 65-70% PHSC. Two, 3, and 5-week-old ia rats were given an intraperitoneal injection of normal bone marrow stem cells (1.4 X 10(4) to 7.0 X 10(4) cells).(ABSTRACT TRUNCATED AT 250 WORDS)
Schneider
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D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods*; D003165:Complement System Proteins / Q000276:immunology; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007518:Isoantibodies / Q000276:immunology; D010010:Osteoclasts / Q000473:pathology; D010022:Osteopetrosis / Q000473:pathology / Q000628:therapy*; D051381:Rats
D007518:Isoantibodies; C035678:anti-Thy antibody; D003165:Complement System Proteins