ABSTRACT
Using an in vivo selection technique, we can isolate individual cells that can repopulate the hematopoietic system of a lethally irradiated murine recipient. These cells rapidly acquire a CD34 phenotype in the animal. Progenitors in our long-term chimeras are of donor type. We also have evidence that transplantation of limiting numbers (as low as a single cell) that have this long-term repopulating ability (LTRA) can self-renew. This is demonstrated by serial transplantation of marrow from engrafted recipients 11 months post transplant into new hosts for four additional months.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells/physiology , Organic Chemicals , Animals , Antigens, CD34/analysis , Bone Marrow/pathology , Cell Division , Cell Movement , Female , Fluorescent Dyes , Graft Survival , Hematopoietic Stem Cells/classification , Hematopoietic Stem Cells/cytology , Immunophenotyping , In Situ Hybridization, Fluorescence , Male , Mice , Radiation ChimeraABSTRACT
Purification of rare hematopoietic stem cell(s) (HSC) to homogeneity is required to study their self-renewal, differentiation, phenotype, and homing. Long-term repopulation (LTR) of irradiated hosts and serial transplantation to secondary hosts represent the gold standard for demonstrating self-renewal and differentiation, the defining properties of HSC. We show that rare cells that home to bone marrow can LTR primary and secondary recipients. During the homing, CD34 and SCA-1 expression increases uniquely on cells that home to marrow. These adult bone marrow cells have tremendous differentiative capacity as they can also differentiate into epithelial cells of the liver, lung, GI tract, and skin. This finding may contribute to clinical treatment of genetic disease or tissue repair.
