Connective tissue progenitors: Practical concepts for clinical applications

Tissue engineering can be defined as any effort to create or induce the formation of a specific tissue in a specific location through the selection and manipulation of cells, matrices, and biologic stimuli. The biologic concepts and the biochemical and biophysical principles on which these efforts are based have become an exciting and rapidly evolving field of biomedical research. More importantly, tissue engineering is becoming a clinical reality in the practice of orthopaedic surgery, providing patients and physicians with an expanding set of practical tools for effective therapy. New and improved matrices and bioactive factors inevitably will play important roles in the evolution of orthopaedic tissue engineering. However, tissue engineering never can stray far from fundamental biologic principles, and one of these is that cells do all the work. No new tissue forms except through the activity of living cells. No bone graft, no matrix, no growth factor, no cytokine can contribute to the generation or integration of new tissue, except through the influence it has on the behavior of cells. The efficacy of all current clinical tools depends entirely on the cells in the grafted site, particularly the small subset of stem cells and progenitor cells that are capable of generating new tissue. The current authors review a series of key biologic concepts related to the rational design and selection of composites of cells and matrices in contemporary bone grafting and tissue engineering efforts. The functional paradigms of stem cell biology are reviewed, including self renewal, asymmetric and symmetric mitosis, and lineage restriction. Several potential sources for autogenous stem cells for connective tissues are discussed. Finally, a simple mathematical model is introduced as a tool for understanding the functional demands placed on stem cells and progenitors in a graft site and to provide a conceptual framework for the rational design of cell matrix composite grafts.