No abstract

High dose chemotherapy (CT) followed by bone marrow transplant (BMT) is increasingly used for the treatment of both hematological and solid neoplasms, but an understanding of its late consequences on the marrow microenvironment is still only at its beginning. It is in fact known that marrow stroma is damaged by high-dose cytotoxic therapy and by radiation exposure. However little is known on the extent of this damage and on the self-repair ability of the stroma. The damage of the stromal microenvironment affects the long-term stem cell engraftment and the maintenance of hemopoietic functions. Furthermore, marrow stroma also represents a progenitor compartment for endosteal osteoblasts, and therefore its damage implies alterations of bone metabolism. Indeed, osteoporosis has recently been recognized as a consequence, of BMT, but only a few studies have been performed to establish the functional status of the stromal compartment after treatment with cytotoxic drugs with or without total body irradiation (TBI) and its role in post-BMT sequelae.

Differentiation of hypertrophic chondrocytes to an osteoblast-like phenotype occurs in vivo in the hypertrophic cartilage of chick embryo tibiae underneath early or prospective periosteum and in cartilage around vascular canals. Synthesis of type I collagen by hypertrophic chondrocytes was shown by immunolocalization of the C propeptide. By enzyme cytochemistry it was instead shown that, in vivo, further differentiating hypertrophic chondrocytes express alkaline phosphatase at the time of initial mineral deposition. Evidence that hypertrophic chondrocytes may resume proliferation was obtained by BrdU labeling. A monoclonal antibody (LA5) was isolated and characterized that recognizes a hypertrophic chondrocyte membrane protein. In addition to staining hypertrophic chondrocytes surrounded by a type II and type X collagen-stainable matrix, the LA5 antibodies also stained elongated chondrocytes at the cartilage/bone collar interface and cells incorporated in the first layer of bone and osteoid matrix.