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 high-risk 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.34 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.

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

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.

Postmenopausal osteoporosis is a high-risk disease that decreases bone strength and makes it easier for patients' bones to be fractured. There are some therapies and medications such as hormone replacement, complementary and alternative medicine, phytohormones, herbal therapies, homeopathy, antidepressants, anticonvulsants, dehydroepiandrosterone to treat postmenopausal osteoporosis. However, some adverse effects have been reported and their uses are limited.17 Therefore, it is important to figure out the trends of research on cell therapy principles and products, and to suggest the direction for improvement and further research on cell therapy for postmenopausal osteoporosis. Mesenchymal stem cells were discovered in 1976, and a method to differentiate mesenchymal stem cells obtained from bone marrow into osteoblasts was developed in the late 1990s. Finally, cell therapy technology for postmenopausal osteoporosis was invented. There are several cell therapy technologies for postmenopausal osteoporosis. Some studies have addressed adoptive transfer of heterogeneous stem cells into humans, whereas others relied on the activation of existing stem cells in human tissue using medication. When heterogeneous stem cells are transplanted into humans, myocyte re-differentiation into adipocytes is induced by PPAR-γ and C/EBP-α, the adipocyte transcription factors. However, further studies regarding signal transduction pathways involved in differentiation are needed. There is a separation and culturing technology that is different from the technology mentioned above and purified mesenchymal stem cells with high differentiation rate. In addition, there are several culture technologies such as single-cell clone separation methods from heterogeneous populations, MACS, and FACS. These technologies are able to solve problems such as changes in cytomorphological features and reduction in differentiation rate and cell proliferation. However, there are other methods that use the surface antibodies stro-1 or sca-1, or changes in medium composition. These technologies, adoptive transfer of heterogeneous stem cells into humans, need more studies to become practically useful. Further studies are required since these technologies are at an early phase of development. There are no cases of commercialization of these technologies or their application to patients. Several problems cause stagnation of the development of these technologies: lack of technologies for mesenchymal stem cell purification and amplification, a small number of studies on the mechanism of differentiation of mesenchymal stem cells into adipocytes and chondrocytes, and the lack of clinical trials in humans. Therefore, further studies are needed to apply these technologies to patients. Once further studies are performed, it would be easier to apply these technologies to postmenopausal patients with gynecological and endocrine-related diseases including osteoporosis.1819 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.