A team of researchers at Johns Hopkins University have defined the roles two types of cells play in bone regeneration, both of which could be used in cellular therapies to speed up the repair of non-healing bone defects
When bone is damaged through trauma, diseases such as cancer, or even due to congenital defects, healing takes place naturally although only for small defects. Beyond a certain size, healing will not take place. Researchers have been studying how bone repair can be augmented and the roles different cells play in bone repair for use in new cellular therapies. Some progress has been made using stem cells derived from fat tissue to stimulate bone formation, but the results have been disappointing.
“A prevailing theory in stem cell therapies derived from fat is that a heterogeneous cell population somehow works in concert to speed tissue regeneration, like different instruments in an orchestra playing in unison,” explained Aaron James, M.D., PhD, associate professor of pathology at Johns Hopkins university School of Medicine and senior author of the study. “But the cellular or molecular mechanisms behind this theory have not been defined.”
The researchers conducted a study to identify the cellular mechanisms involved and attempted to isolate subpopulations of cells to determine which are most effective at promoting bone repair. The researchers identified two types of cells found in the vessel walls of adipose tissue which play an important role in bone repair, both of which could be used for cellular therapy to treat bone defects and non-healing bone injuries.
Both types of cells were isolated from human tissue taken from liposuction specimens which were used on their own and in combination on mice with non-healing skull defects. The same amounts of each perivascular stem cell type were used singularly and in a 50/50 combination and the researchers measured the amount of bone growth using micro CT imaging before treatment and 8 weeks after the cells were introduced.
When used singularly there was patchy bone formation. When used in combination there was more robust bone formation. The cells therefore work in tandem to promote bone formation, but each has a distinct role in the process. In vitro lab tests revealed the different role each plays in the process. Pericytes were found to induce the growth of new blood vessels while adventicytes induced the formation of bone cells called osteoblasts.
It is not yet known is what concentration of each cell type is required to achieve the best results. Work is continuing to determine the optimum ratio of the two cell types to achieve the maximum rate of bone growth.
The study is detailed in the paper – Relative contributions of adipose-resident CD146+ pericytes and CD34+ adventitial progenitor cells in bone tissue engineering – which was recently published in the journal npj Regenerative Medicine. DOI: 10.1038/s41536-018-0063-2