Circulating CD14⁺ monocytes originate from hematopietic stem cells and are believed to be committed precursors for phagocytes such as macrophages. Recently, we have reported a primitive human cell population called monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology in culture and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. MOMCs are derived from circulating CD14⁺ monocytes, but circulating precursors still remain undetermined. MOMCs contain progenitors with the capacity to differentiate into a variety of mesenchymal cells in vitro, including bone, cartilage, fat, and skeletal and smooth muscles. Moreover, MOMCs are able to differentiate into the cardiomyogenic and neuronal lineage by co-culturing with primary cultures of embryonic heart and brain, respectively. In addition, MOMCs have capacity of differentiating into endothelium of a mature phenotype with typical morphologic, phenotypic, and functional characteristics. In vitro generation of MOMCs from precursors within circulating monocytes requires their binding to fibronectin and exposure to soluble factors derived from activated platelets. In a rat model of cerebral ischemia, transplantation of MOMCs into the ischemic core results in a significant improvement in neurologic function, but this effect is primarily due to neovascularization through production of a large array of angiogenic factors by MOMCs with some contribution of their differentiation into mature endothelial cells. These findings indicate that circulating CD14⁺ monocytes are involved in a variety of physiologic functions other than innate and acquired immune responses, such as repair and regeneration of the damaged tissue, through a variety of mechanisms.

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“Stem cells” is the general term for cells that have the ability to renew themselves and the ability to differentiate into the cells that compose tissues. Stem cells possess a combination of “pluripotentiality”, which is the source of their ability to differentiate into various cell types that compose tissues and to fulfill their functions, and “self-renewal” ability, which replenishes “stem cells” themselves in the undifferentiated state by cell division.
Stem cells or undifferentiated cells in vertebrates^1-4), are broadly classified into two types: stem cells in the embryo stage, and adult stem cells, which are present in the tissues of adults. When organs are formed during embryonic stage, organogenesis is achieved by vigorous renewal by embryonic stem (ES) cells, which have very high proliferative capacity, and by orderly differentiation of tissue cell groups (patterning)^1-4). ES cells are cells in the initial state when the fertilized egg is in the process of dividing, and since they harbor the ability to become any stem cells required for embryonic tissue-patterning, they are also called pluripotent stem cells. Induced pluripotent stem cells (iPS cells)^{5, 6)} are artificially produced stem cells that are endowed with the same pluripotency to differentiate as these ES cells. In theory, cells that possess this pluripotency are able to differentiate into the constituent cells of every organ and tissue in the body. Therefore transplantation-based therapeutic application by using autologous cells as the source of production of iPS cells came closer to becoming a reality. Furthermore, established iPS cells from various diseases can also provide human stem cell resources for pharmacological, diagnostic or genetic evaluation.

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Since the success of imatinib in the treatment of chronic myeloid leukemia, tyrosine kinaseinhibitors have been shown to be both efficacious and well tolerated despite absolute specificityfor a single kinase. Consequently, multiple tyrosine kinase inhibitors have been approved andmany more are in development. The JAK family of tyrosine kinases consists of 4 cytoplasmicproteins, which are obligatorily required for Type I/II cytokine receptors to signal and activateintracellular signaling pathways. They are critical for the function of over 60 cytokines and aretherefore attractive targets for the generation of new immunomodulatory and oncology drugs.

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Thymic stromal lymphopoietin (TSLP) is recently implicated as a key molecule for initiating allergic inflammation at the epithelial cell-dendritic cell (DC) interface. TSLP is produced predominantly by epithelial cells, and induces the production of multiple chemokines and cytokines by several innate cell types such as DCs, mast cells, eosinophils, and NKT cells, contributing to the innate phase of allergic inflammation. However, its function is more prominent in the DC-mediated adaptive phase of allergic inflammation. TSLP-activated myeloid DCs (mDCs) can promote naïve CD4⁺ T cells to differentiate into a Th2 phenotype. We analyzed the signal transduction mechanisms of TSLP in human primary mDCs and found that it potently transduces a unique Th2-inducing compound signal in DCs. Whereas activation of nuclear factor κB (predominantly p50) drives DCs to produce OX40L to induce Th2 differentiation, the activation of signal transducer and activator of transcription 6 (STAT6) triggers DCs to secrete chemokines necessary for the recruitment of Th2 cells. In addition, TSLP signaling limits the activation of STAT4 and interferon regulatory factor 8 (IRF8), which are essential factors for the production of the Th1-polarizing cytokine interleukin-12. Because TSLP can be a rational therapeutic target for the treatment of allergic disorders, elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype is essential for developing anti-TSLP therapy.

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Although the role of p16^INK4a tumor suppressor gene expression is well documented in various cell culture studies, its in vivo roles are poorly understood. To gain further insight into the roles and mechanisms regulating p16^INK4a gene expression in vivo, we attempted to visualize the dynamics of p16^INK4a gene expression using bioluminescence in vivo imaging technique in living mice. By monitoring and quantifying the p16^INK4a gene expression repeatedly in the same mouse throughout its entire lifespan, we were able to unveil the dynamics of p16^INK4a gene expression in the aging process. This system can also be applied to chemically- or genetically- induced carcinogenesis. Here, we introduce you a novel approach to study senescence stress response in vivo and its potential towards understanding molecular link between aging and cancer.

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