Bone production by stem cells is usually the domain of bone marrow-derived stem cells. However, fat-derived stem cells can make bone in culture, although they do not seem to be as efficient at making bone as bone marrow stem cells. Nevertheless, some enterprising stem cells scientists have designed protocols for using purified adipose-derived stem cells to make high quality bone tissue faster than the currently-used methods. The new technology may someday eliminate the need for painful bone grafts that use material taken from the patient during invasive procedures.
Fat is thought to be an ideal source of MSCs, since they are plentiful and easily acquired by liposuction.
Traditionally, cells taken from fat had to be grown in culture for weeks in order to isolate the bone-making stem cells. Unfortunately, the expansion of these cells increases the risk of infection and genetic instability. However, a fresh, non-cultured cell composition called stromal vascular fraction (SVF) is also used to grow bone, but SVF cells extracted from fat constitute a highly heterogeneous population that includes cells that do not have the ability to make bone.
To solve this problem, researchers used a cell sorting machine to isolate and purify human perivascular stem cells (hPSC) from adipose tissue and demonstrated that these purified cells worked far better than SVF cells in bone-making assays. In addition, they also showed that a growth factor called NELL-1 enhanced bone formation in their animal model.
According to Dr. Chia Soo, vice chairman for research at UCLA Plastic and Reconstructive Surgery, who was involved with this study: “People have shown that culture-derived cells could grow bone, but these are a fresh cell population and we didn’t have to go through the culture process, which can take weeks. The best bone graft is still your own bone, but that is in limited supply and sometimes not of good quality. What we show here is a faster and better way to create bone that could have clinical applications.”
In the animal model, Soo and colleague Bruno Pйault placed hPSCs with NELL-1 in a muscle pouch (a location where bone normally does not grow). They then used X-rays to show that the cells did indeed become bone.
“The purified human hPSCs formed significantly more bone in comparison to the SVF by all parameters,” Soo said. “And these cells are plentiful enough that patients with not much excess body fat can donate their own fat tissue.”
Conceivably, patients may one day have rapid access to high-quality bone graft material by which doctors extract some of the patient’s fat tissue, purify the hPSCs from it, and then replace their own stem cells with NELL-1 back into the area where bone is required. The hPSCs cultured with NELL-1 could grow into bone inside the patient, which eliminates the need for painful bone graft harvestings. The goal is to isolate the hPSCs and add the NELL-1 with a matrix or scaffold in order to aid cell adhesion, all in less than an hour.
“Recent studies have already demonstrated the utility of perivascular stem cells for regeneration of disparate tissue types, including skeletal muscle, lung and even myocardium,” said Pйault, a professor of orthopedic surgery at UCLA. “Further studies will extend our findings and apply the robust osteogenic potential of hPSCs to the healing of bone defects.”