Directing stem cells to travel and adhere to the surface of bone for bone formation has been among the elusive goals in regenerative medicine.
This new method enhances bone growth by using a unique hybrid molecule, LLP2A-alendronate. When injected into the bloodstream LLP2A-alendronate directs the body's stem cells to travel to the surface of bones. Once there the stem cells differentiate into bone-forming cells and synthesize proteins to enhance bone growth.
"There are many stem cells, even in elderly people, but they do not readily migrate to bone," said Wei Yao M.D., Assistant Professor, Center for Aging, UC Davis. "Finding a molecule that attaches to stem cells and guides them to the targets we need is a real breakthrough."
After the hybrid molecule is injected into the bloodstream it picks up mesenchymal stem cells in the bone marrow and directs those cells to the surfaces of bone where the stem cells carry out their natural bone-formation and repair functions.
"Our study confirms that stem-cell-binding molecules can be exploited to direct stem cells to therapeutic sites inside an animal," said Lam. "It represents a very important step in making this type of stem cell therapy a reality."
Twelve weeks after the hybrid molecule was injected into mice, bone mass in the femur (thigh bone) and vertebrae (in the spine) increased and bone strength improved compared to control mice who did not receive the hybrid molecule. Treated mice that were normally of an age when bone loss would occur also had improved bone formation, as did those that were models for menopause.
Alendronate, also known by the brand name Fosamax, is commonly taken by women with osteoporosis to reduce the risk of fracture. The research team incorporated alendronate into the hybrid molecules because once in the bloodstream it goes directly to the bone surface, where it slows the rate of bone breakdown. According to Nancy Lane, Director of the UC Davis Musculoskeletal Diseases of Aging Research Group, the dose of alendronate in the hybrid compound was low and unlikely to have inhibited the compound's therapeutic effect.
Lane, an Endowed Professor of Medicine and Rheumatology and an expert on osteoporosis, added, "For the first time, we may have potentially found a way to direct a person's own stem cells to the bone surface where they can regenerate bone. This technique could become a revolutionary new therapy for osteoporosis as well as for other conditions that require new bone formation."
Osteoporosis is a major public health problem for 44 million Americans. One in two women will suffer a fracture due to osteoporosis in their lifetime. Although effective medications are available to help prevent fracture risk, including alendronate, their use is limited by potential harmful effects of long-term use.
The major causes for osteoporosis in women include estrogen deficiency, aging and steroid excess from treatment of chronic inflammatory conditions such as rheumatoid arthritis. Generally, the osteoporosis generated by these metabolic conditions results from change in the bone remodeling cycle that weakens the bone's architecture and increases fracture risk.
Mesenchymal stem cells from bone marrow induce new bone remodeling, which thicken and strengthen bone.
The researchers noted that potential use of this stem cell therapy is not limited to treating osteoporosis. It may prove invaluable for other disorders and conditions that could benefit from enhanced bone rebuilding, such as bone fractures, bone infections or cancer treatments.
Adapted from the UC Davis Health System Announcement.
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