Osteoporosis Treatment: a guide for stem cells
A unique hybrid molecule for the treatment of osteoporosis with stem cells has been developed
Nanonewsnet based on materials from the University of California – Davis:
UC Davis investigators develop method of directing stem cells to increase bone formation and bone strengthA group of researchers led by scientists from the University of California at Davis has developed a new method of stimulating bone growth using a molecule that, when injected into the blood, directs bone marrow stem cells to their surface.
Upon reaching the bone surface, stem cells differentiate into bone-forming cells and synthesize proteins that enhance its growth. In a study published in the journal Nature Medicine (Min Guan et al., Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass), scientists used a mouse model of osteoporosis to demonstrate a unique treatment approach that increases bone density and prevents bone loss associated with aging and bone deficiency the body of female sex hormones estrogens.
"Even the elderly have a lot of stem cells, but they do not readily migrate to the bones," says lead author of the study Wei Yao (Wei Yao). "The development of a molecule that binds to stem cells and directs them to the target we need is a real breakthrough."
Scientists are studying stem cells as a possible method of treating a wide range of diseases and injuries – from peripheral artery damage and macular degeneration to blood and organ diseases and skin wounds. However, forcing stem cells to migrate to the surface of bones and stimulate their growth has long remained one of the unattainable goals of regenerative medicine.
American scientists used a unique hybrid molecule, LLP2A-alendronate, developed by a group led by Kit Lam, professor and head of the Department of Biochemistry and Molecular Medicine at UC Davis.
The hybrid molecule consists of two parts: a synthetic ligand molecule LLP2A (structural formula on the left - VM), binding to mesenchymal stem cells in the bone marrow, and the second part, consisting of a "self–guided" drug for the treatment of bones – alendronate (right). After injection into the blood, the hybrid molecule binds to mesenchymal stem cells in the bone marrow and directs these cells to the surface of the bones, where they perform their natural functions – the formation and restoration of bone tissue.
"Our study confirms that molecules binding to stem cells can be used to direct them to animal organs in need of treatment," Professor Lam comments on the work. "This is a very important step towards making this type of stem cell treatment a reality."
Bone mass and strength of the femur and spine of mice increased twelve weeks after the introduction of hybrid molecules. Positive bone processes occurred both in mice at the age of active bone loss and in animals with a menopausal model.
Alendronate, also known under the brand name Fosamax, is usually prescribed to women with osteoporosis to reduce the risk of fractures. Scientists have included alendronate in the hybrid molecule because, once in the blood, it goes directly to the surface of the bones and slows down the rate of their destruction. According to study co-author Nancy Lane, the dose of alendronate in a hybrid compound is low and is unlikely to reduce its therapeutic effect.
"For the first time, we may have found a potential way to direct a patient's own stem cells to the bone surface, where they can repair it," says Lane, professor of medicine and rheumatology, an osteoporosis specialist. "This method can revolutionize the treatment of osteoporosis, as well as other diseases requiring the formation of new bone tissue."
Osteoporosis is one of the main public health problems, given the fact that 44 million American women suffer from it in the United States alone. Despite the availability of effective medications that can reduce the risk of fractures, including alendronate, their use is limited by the potentially dangerous consequences of long-term use.
Aging reduces the number of mesenchymal stem cells (MSCs) differentiating in the bone marrow into osteoblasts, which leads to a violation of osteogenesis. Stimulation of the differentiation of MSCs in the osteogenic direction could become a reliable way of bone regeneration. Scientists have developed a method that allows to direct MSCs to the bone surface by attaching a synthetic ligand-peptidomimetic (LLP2A) with high affinity and specificity to the protein integrin α4ß1 on the surface of MSCs to bisphosphonate (alendronate, Ale) with high affinity to bone tissue. The hybrid molecule LLP2A-Ale induces MSCs migration and osteogenic differentiation in vitro. One intravenous injection of LLP2A-Ale enhances the formation of spongy bone and bone mass both in xenotransplantation studies and in immunocompetent mice. In addition, LLP2A-Ale prevents age-related and estrogen-deficiency-induced loss of trabecular bone mass. These results are proof of the principle that LLP2A-Ale can guide MSCs to bone and stimulate the formation of new bone tissue and increase bone strength.
The image shows bone marrow stem cells grown in an osteogenic medium (control) and with LLP2A-Ale.
Colony-forming fibroblastic cells (CFU-F) are colored purple,
colony-forming osteoblasts (CFU-Ob), CFU–F subpopulation, - red
(Photo: nature.com )
The main causes of osteoporosis in women are estrogen deficiency, aging and an excess of steroids as a result of the treatment of chronic inflammatory diseases such as rheumatoid arthritis. As a rule, osteoporosis caused by these metabolic diseases develops as a result of changes in the cycle of bone remodeling, which weaken the architecture of the bone and increase the risk of fractures.
Scientists note that the use of this method of regenerative medicine is not limited to osteoporosis therapy. It can be invaluable for other disorders and diseases when it is necessary to strengthen the restoration of bone tissue, for example, fractures, bone infections or cancer.
According to one of the study participants, the director of the Institute for Regenerative Cures at UC Davis, Jena Nolta, the results obtained are very promising from the point of view of their clinical application. "We have shown the effectiveness of this potential therapy method in rodents, and now our goal is to move on to its clinical trials."
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16.02.2012