Updated on 12 June 2012
"The main problem is this makeup of heterogeneous cell population, which can lead to unreliable bone formation," Dr Chia Soo explained. She and Dr Bruno Péault, and Dr Kang Ting were the senior corresponding investigators on the study, funded by the California Institute of Regenerative Medicine.
So, the UCLA team decided to see what would happen if they purified the SVF cells to reduce their inherent heterogeneity and obtain a safer, more efficient stem cell-based therapeutic. Their goal was to isolate a population of stem cells known as perivascular stem cells (PSCs) that surround blood vessels. The team then took the bone grafts grown from the human PSCs and implanted them in mice to compare their bone-forming capacity with that of traditionally derived SVF.
The results exceeded expectation. "The purified human PSCs formed significantly more bone in comparison to traditionally derived SVF by all parameters," Dr Aaron James, the study's lead author. "This is true in terms of potency, identity and purity."
The human PSCs also appear to be more predictable than SVFs. "Moreover," Dr Péault added, "human PSCs are plentiful within adipose tissue so that even patients with minimal excess body fat can donate their own fat tissue for harvesting the cells. As an added bonus, the PSCs do not need to be cultured in the laboratory, which cuts down on the time and cost needed to produce them while also reducing the risk of immunogenicity, infection and genetic instability."
At the same time, the researchers looked at growth factors for the human PSCs that would speed up the bone production. They focused on two candidates: BMP2 (bone morphogenetic protein2) and NELL-1 (Nel-like molecule-1), a potent bone-forming molecule first described by Dr. Ting. The mice whose implants were treated with NELL-1 showed a significant increase in the amount of therapeutically sound bone tissue produced, while those with BMP2-treated cells exhibited drawbacks including cyst-like bone formations or fat tissue.
"This research team has successfully addressed some of the hurdles with using fat tissue as a source of stem cells for bone formation," said Dr Anthony Atala, editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "The possibility of using this method in the future to heal bone defects would be a breakthrough for patients."