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Cell Therapy Products in Menopausal Medicine

The incidence of postmenopausal diseases increases with the age of women. In this review, we introduce cell therapy products, a new treatment for postmenopausal osteoporosis, which often occurs in postmenopausal women. We also figure out the trends of research on cell therapy products and emphasize the necessity and importance of this research for researchers and postmenopausal women. Finally, we suggest the direction for improvement of postmenopausal osteoporosis and research on cell therapy products. We investigated which medication have been used so far. We also examined the development and technical problems of technologies that are currently in use.


Introduction
The average life expectancy has been increasing constantly due to technical developments in medicine, industry, and science. The average life expectancy appears to be longer in women than in men. The average life expectancy of Korean women was 85.5 years in 2014, which was 0.84 years higher than in 2012. Consequently, the incidence of diseases related to aging in women and interest in studying and finding treatments for these diseases have been also increasing. 1 Especially, postmenopausal osteoporosis, the main disease related to aging in women, is a highrisk disease that decreases bone strength and makes it easier for patients' bones to be fractured. 2 Currently, most medications for postmenopausal osteoporosis suppress activity of osteoclasts and cause adverse effects. 3,4 Most widely used medications for postmenopausal osteoporosis are oral and intravenous bisphosphonates, such as alendronate, ibandronate, risedronate, and zoledronate. However, despite their proven safety and efficacy, adverse events such as upper gastrointestinal, impaired renal function, fever, osteonecrosis of jaw, uveitis, and atrial fibrillations have been reported, and thereby their use is limited. 5 However, cell therapy products could be a new treatment which reduces the possibility of adverse effects and used widely, unlike existing medication treatments. We reviewed history, research and development (R & D) of cell therapy products for postmenopausal osteoporosis, and examined current problems. We also suggest how cell therapy could be improved.

Development of Cell Therapy Products for the Treatment of Postmenopausal Osteoporosis
In 1976, Friedenstein proved that there is a possibility that mesenchymal stem cells exist in bone marrow. In the late 1990s, technology to differentiate mesenchymal stem cells from human bone marrow into osteoblasts was established, and many studies based on this technology have been conducted. 6 Several studies have improved the osteoblast differentiation method using various active substances.
There have also been some studies on bone formation by extracting mesenchymal stem cells from tissues other than bone marrow and an attempt to replace the cells alone to existing biological tissue engineering method. However, applying these methods to clinical research is still in the early stages. 7

Technologies and Principles of Cell Therapy Products in Postmenopausal Osteoporosis
Most studies on stem cell applications likely aim to advance fundamental knowledge. However, phased studies that aim to develop a cell therapy product are in progress and bring them to the market. These cells can be isolated not only from bone marrow, but also from peripheral blood and umbilical cord blood. 12,13 Studies of cell surface antibody suggested that mesenchymal stem cells could be purified by using magnetic-activated cell sorting (MACS) or fluorescence-activated cell sorting (FACS).
However, more studies of representative surface antigens are needed. 14

Lack of clinical trials
There have been animal studies that reported transplantation of stem cells originated from bone marrow to treat musculoskeletal system defects such as spondylodesis and arthritis, and to reconstruct skull bone defects, local defects of joint cartilage, and tendon defects. 13  Once further studies are performed, it would be easier to apply these technologies to postmenopausal patients with gynecological and endocrine-related diseases including osteoporosis. 18,19 Consequently, the quality of life in elderly women as well as postmenopausal women will improve. We perform this study so that scientists as well as physicians pay attention to cell therapy technology and applying cell therapy technology to menopausal medicine.