The finding may one day eliminate the need for painful bone grafts that use material taken from patients during invasive procedures.
Adipose, or fat, tissue is thought to be an ideal source of mesenchymal stem cells — cells capable of developing into bone, cartilage, muscle and other tissues — because such cells are plentiful in the tissue and easily obtained through procedures like liposuction, said Dr. Chia Soo, vice chair of research for the UCLA Division of Plastic and Reconstructive Surgery.
Soo and Bruno Péault, the co-senior authors on the project, are members of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
Traditionally, cells taken from fat had to be cultured for weeks to isolate the stem cells which could become bone, and their expansion increases the risk of infection and genetic instability. A fresh, non-cultured cell composition called stromal vascular fraction (SVF) also is used to grow bone. However, SVF cells taken from adipose tissue are a highly heterogeneous population that includes cells that aren't capable of becoming bone.
Péault and Soo's team used a cell-sorting machine to isolate and purify human perivascular stem cells (hPSC) from adipose tissue and showed that those cells worked far better than SVF cells in creating bone. They also showed that a growth factor called NELL-1, discovered by Dr. Kang Ting of the UCLA School of Dentistry, enhanced bone formation in their animal model.
"People have shown that culture-derived cells could grow bone, but ours are a fresh cell population, and we didn't have to go through the culture process, which can take weeks," Soo said. "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."
The study was published Monday (June 11) in the early online edition of Stem Cells Translational Medicine, a new peer-reviewed journal that seeks to bridge stem cell research and clinical trials.
In the animal model, Soo and Péault's team put the hPSCs with NELL-1 in a muscle pouch, a place where bone is not normally grown. They then used X-rays to determine 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."
Soo said that if everything goes well, patients may one day have rapid access to high-quality bone graft material: Doctors will get their fat tissue, purify that into hPSCs, and replace the patient's own stem cells with hPSCs and NELL-1 in the area where bone is required.
The hPSCs with NELL-1 could grow into bone inside the patient, eliminating the need for painful bone-graft harvestings. The goal is for the process to isolate the hPSCs and add the NELL-1 with a matrix or scaffold to aid cell adhesion in less than an hour, Soo said.
"Excitingly, 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 Péault, a UCLA professor of orthopedic surgery "Further studies will extend our findings and apply the robust osteogenic potential of hPSCs to the healing of bone defects."
The study was funded in part by the California Institute of Regenerative Medicine's Early Translational Research Award and Training Grant Research Fellowship; a University of California Discovery Grant; and the National Institute of Dental and Craniofacial Research Center at the National Institutes of Health (R21-DE0177711 and RO1-DE01607).
The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research: UCLA's stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Broad Stem Cell Research Center is committed to a multidisciplinary, integrated collaboration among scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed toward future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine at UCLA, UCLA's Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.