Osteogenesis from Pluripotent Stem Cells: Neural Crest or Mesodermal Origin?

Abstract

Research in stem cell biology has the potential to dramatically alter the way we understand the vast complexity and coordination that is required for an organism to develop and function. The creation of therapeutic tools that will inevitably accompany these discoveries in this field of research may completely revolutionize our approach to medicine in the 21st century. In this chapter we will examine one facet of stem cell research that holds great potential to improve the quality of life for millions of individuals; the study of osteogenesis from pluripotent stem cells. Despite its overt rigid structure, which provides mechanical support and protective functions, bone is a highly dynamic tissue that is tightly regulated to serve multiple roles in the body. Bone tissue is constantly being remodeled by the actions of the osteoblasts, the bone forming cells, and the osteoclasts, the bone resorbing cells. The improper balance of these cells can result in a number of bone-related and osteodegenerative diseases. Osteoporosis, for example, is estimated to effect 75 million individuals in Europe, Japan and the US alone, and thus the potential benefits of understanding the processes regulating osteogenesis may be quite far reaching. Despite the similarity of the bone tissues found in the adult mammalian skeleton, there are three different sources from which bone is derived in the developing embryo (Fig. 1). Two of these bone origins are from mesodermal progenitors, where cells from either the lateral plate or paraxial mesoderm contribute to the appendicular or axial skeleton, respectively. The third origin of bone tissue can be traced back to ectodermal cells where neural crest progenitors differentiate into many of the bones within the craniofacial region. Differences in the origin in bone are also paralleled in differences seen in the bone formation process. Most bones of mesodermal origin develop via the process of endochondral bone formation, whereas the bones of ectodermal origin form by a process called intramembranous bone formation. These processes differ most generally in the series of cell differentiations that lead to the mature tissue. In endochondral bone formation the mesenchymal progenitors differentiate into chondrocytes, which lay down the cartilaginous framework that is eventually replaced by the mineralized matrix of invading osteoblasts, while the chondrocytes undergo apoptosis. In intramembranous bone formation, the progenitors differentiate directly into osteoblasts. In addition, mature bone tissues house adult stem cell niches, such as those composed of mesenchymal or hematopoietic stem cells. These cells are