Stem cells from fat tissue can grow bone for grafts
15 June 2012
Bone grafts grown from purified stem cells originating from a
patient's own fat tissue could lead to a more efficient way to
regenerate bone and end the painful operations needed to collect a
patient’s own bone for grafting. The results could have significant
impact on those suffering from severe bone injuries or disease.
In a study published in the June issue of Stem Cells
Translational Medicine, researchers were able to demonstrate the
potential of a population of stem cells found in human fat to generate
bone. They also identified a new factor to stimulate bone growth. The
team was made up of scientists from the UCLA-Orthopaedic Hospital
Department of Orthopaedic Surgery, the Orthopaedic Hospital Research
Center, and the Eli and Edythe Broad Center of Regenerative Medicine and
Stem Cell Research at the University of California-Los Angeles (UCLA).
Researchers have long recognized the potential of stem cells
harvested from fat — which they call “adipose-derived stem cells” or
ASCs — in bone engineering. For one thing, stem cells are more easily
obtainable from fat than from bone marrow, which also contains stem
cells, plus ASCs have already been used successfully to heal skeletal
defects in animals. And while the current gold standard for collecting
bone for grafting — “autograft bone,” which is that taken from the
patient himself — has significant disadvantages, including the potential
for complications arising from the extended operating time needed to
collect it, harvesting stem cells from fat tissue is painless and poses
minimal risk to the patient.
However, there are several obstacles
to the use of ASCs, including the risk of infection and genetic
instability when the cells are isolated and expanded in the lab. As an
alternative, researchers have looked at the possibility of using stromal
vascular fraction (SVF), which comes from lipoaspirate, the byproduct of
a liposuction.
SVF contains a variety of cells, including smooth
muscle cells, fibroblasts, adult stem cells and more. In addition, it
contains blood cells from the capillaries supplying the fat cells. The
SVF has the advantage of being rapidly available (there is no need for
culture isolation), but it falls significantly short for bone growth,
with studies showing it yields poor and unreliable bone formation.
“The main problem is this makeup of heterogeneous cell population,
which can lead to unreliable bone formation,” Chia Soo, M.D., explained.
She and Bruno Péault, Ph.D., and Kang Ting, D.M.D., D.Med.Sc., were the
senior corresponding investigators on the study, funded by the
California Institute of Regenerative Medicine (CIRM).
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.
Exceeding expectation
“The purified human PSCs formed significantly more bone in
comparison to traditionally derived SVF by all parameters,” Aaron James,
M.D., the study’s lead author, said. “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.
“The marriage
of a competent cell source for growing bones with an efficient growth
factor is a logical union for skeletal tissue engineering,” Drs Soo,
Péault, and Ting concluded. “We believe our study demonstrates an
optimal combination product for local bone formation in patients.”
“This research team has successfully addressed some of the hurdles
with using fat tissue as a source of stem cells for bone formation,”
said Anthony Atala MD, 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.”