Takahiro Ochiya

Therapeutic Application of MicroRNAs in Cancer

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression thereby controlling many biological and cellular processes, including development, organogenesis, and homeostasis. Due to miRNAs ability to target multiple mRNAs, if miRNA expression is altered, diseases such as cancer can occur as a consequence of the misregulation of target gene networks. Deregulation of miRNA expression in cancer cells is caused by a variety of mechanisms such as genetic alterations, epigenetic regulation, or altered expression of transcription factors, which target miRNAs. Many recent studies have focused on the development of novel diagnostic tools and therapeutics in the field of oncology. In this chapter, we summarize the latest and most significant discoveries for the use of miRNA-based therapy in various physiological and pathological conditions with particular focus on cancer. In addition, we discuss a new method for the delivery of miRNA to a desired site using biologically significant exosomes.

Circulating microRNAs as Hormones: Intercellular and Inter-organ Conveyors of Epigenetic Information?

The discovery of microRNAs (miRNAs) has created a paradigm shift not only in the traditional central dogma of molecular biology but also in the research of a variety of human diseases. Fourteen years after the discovery of miRNAs, there was another revolutionary finding: cells can shuttle miRNAs between each other via small lipid bilayer vesicles called exosomes. This exosome-mediated horizontal transfer of genetically encoded messages is now recognized as a means of intercellular communication. This chapter reviews the concept that miRNAs can function as hormones conveying epigenetic information.

Exploration for Cell Sources for Liver Regenerative Medicine: “CLiP” as a Dawn of Cell Transplantation Therapy

Abstract Orthotropic liver transplantation is the only current therapy for serious liver disease, but its application is limited due to a shortage of donors. Cell transplantation has been proposed as an alternative treatment for end-stage liver disease to overcome this obstacle. However, cell transplantation therapy is hampered due to the shortage of fully functional cell sources. In this chapter, we present an overview of the present situation and issues regarding cell transplantation therapy and introduce a new candidate cell source named chemically induced liver progenitors (CLiPs), which we have recently characterized. We also discuss the potential uses and limitations of CLiP technology for cell transplantation therapy, such as the generation of human CLiPs, as well as future perspectives.