Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis

Inflammation, cartilage and bone erosions, joint destruction--that's the typical progression of arthritis and most rheumatic diseases.

While inflammation may be controlled, and perhaps even eliminated, with early aggressive treatment, few therapeutic approaches offer hope for repairing tissue once the damage has been done. One promising strategy is the use of mesenchymal stem cells (MSCs). MSCs are capable of extensive self-renewal and adaptable to forming all kinds of connective tissues. While detected in several adult human tissues, MSCs have traditionally been obtained from bone marrow, an invasive, painful, and costly process.

Researchers in the United Kingdom and Belgium set out to investigate the characteristics of cells in the periosteum, the dense membrane at the boundary between the bone and the surrounding soft tissues. Their study, featured in the April 2006 issue of Arthritis & Rheumatism, is the first to identify periosteal cells as MSCs, with multipotent properties at the single cell level and the potential to regenerate cartilage, muscle, and bone in patients with inflammatory and degenerative rheumatic diseases.

Samples of periosteal cells were obtained from the tibia of 12 human donors, ranging in age from 24 to 83 years. Following enzymatic release and culture expansion, cell populations were tested for telltale markers of MSCs, as well as for their growth and differentiation potential. To assess their multipotency beyond the laboratory, the periosteal cells were then injected into one of three animal models: mice, with the goal of muscle regeneration; goats, with the goal of developing cartilage; and mice, with the goal of bone formation.

Regardless of donor age, periosteal cells expanded extensively, steadily maintaining growth curves over at least 30 population doublings. They also displayed the hallmarks of MSCs, including long telomeres, the sections of DNA at the end of a chromosome. What's more, the results of the animal experiments proved that expanded periosteal MSCs can contribute to muscle regeneration and form cartilage when implanted into a joint surface defect. The bone tissue retrieved from the last group of mice was partly human, which indicates the potential of these cells to build bone as well.

"Like MSCs derived from bone marrow, periosteal MSCs rapidly adhere to plastic and can be expanded for several passages, preserving their multipotency," notes study leader Dr. Cosimo De Bari, an MRC clinician scientist and consultant rheumatologist at King's College London, UK. "A small periosteal biopsy represents a relatively easily accessible source of MSCs."

This groundbreaking study calls attention to the need for more research into MSCs--in the periosteum and other tissues--and their practical therapeutic benefits for late-stage arthritis sufferers.