Derivation and Characterization of Bone Cells from Human Umbilical Cord Blood and Harakiri Deficient Mice

Abstract

There is a growing need for bone cells to be used in the generation and repair of bone tissues that have become destroyed as a result of disease (e.g. osteoporosis), injuries and genetic deficiencies. Human umbilical cord blood has been a source of cells that is being investigated for its ability to generate cells for repair of various tissues including bone, which is the focus of this investigation. Similarly cord blood can also be used as a source of progenitors for osteoclasts that might be used for management of other diseases of bone characterized by defects in these cells (e.g. osteopetrosis). Moreover, there are few reliable in vitro models for human osteoclasts and so the ability to develop a cell model for human osteoclasts will also permit more meaningful studies on regulation of these cells than possible in the past. One of the setbacks suffered by researchers in designing therapeutic uses for stem cells is that in laboratory animals tumours can arise from these transplanted and pleuripotential cells. This suggests that stem cells might also have a dysregulated apoptosis pathway, which is critically important to understand before the safe use of stem cells can be assured. In order to increase our understanding of apoptosis in bone cells in particular, studies were done to try to understand the role of harakiri, a pro-apoptotic gene, in the development of osteoblasts and osteoclasts. Therefore, this series of study had two main foci; the development of human bone cells, particularly osteoclasts and osteoblasts, from human umbilical cord blood, and to understand further the mechanisms regulating apoptosis in bone cells. This study showed that osteoblasts could not be derived easily from human cord blood cells while it was possible to generate fully functional osteoclasts, which demonstrated unique properties. Studies done on harakiri deficient mice showed that absence of this gene caused an increase in osteoblast formation and a decrease in osteoclast formation. These findings can be exploited when considering the development of pharmacological agents that might be used in the future to modulate osteoclast cell development, function, and apoptosis.