Cell-based tissue engineering therapies: the influence of whole body physiology

A technology has been developed to isolate a developmentally and phenotypically homogeneous population of pluripotent human mesenchymal stem cells (hMSCs) from adult bone marrow and mitotically expand these cells in culture. These hMSCs have osteoblasts as one of their potential developmental end-stage phenotypes, and, in addition to their osteogenic potential, these hMSCs synthesize and secrete a variety of macromolecules that are known regulators of osteoclast differentiation and activity. In this review, data are presented that demonstrate the phenotypic and developmental homogeneity of the cells in hMSC cultures, as well as their ability to differentiate along multiple phenotypic pathways and serve as regulatory cells for hematopoietic and bone-resorbing cells. In addition, a logic and preliminary data are presented that support the use of hMSCs in the prevention and treatment of age-related and postmenopausal osteoporosis. Since hMSC differentiation and phenotypic expression are controlled by regulatory molecules synthesized and secreted by a variety of local and systemic mechanisms, the issue of whole organism physiology is addressed in considering tissue engineering logics.