We have recently developed the concept of “designer molecules,” which are capable of adding various new functions to cells. Designer molecules consist of a “cell anchor moiety” for immobilization to the cell membrane, a “functional moiety” for adding function, and a “stealth moiety” for evading immune cells. As proof of concept, we synthesized a designer molecule that allows target-directionality and subsequently demonstrated its efficacy. Designer molecules are expected to be applied as a unique strategy that can add various functions to cells through chemical approaches.

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The treatment landscape for malignant tumors, particularly solid tumors, has undergone profound shifts with the emergence and development of molecularly targeted therapies and advanced immunotherapeutic agents. These innovative approaches have contributed to steadily improving therapeutic outcomes, and in many cases, early detection paired with prompt intervention has enabled curative treatment. However, malignant tumors remain the leading cause of mortality in Japan - a reflection of the limited success in treating certain cancer types despite advances in technology and therapeutics. At the forefront of therapeutic technology development, significant efforts are being devoted to enhancing the functionality of cell-based therapeutics. This article focuses particularly on surface modifications applied to cells without genetic modifications. We hope it will contribute to a deeper understanding of the mechanisms of action and therapeutic strategies of newly emerging agents, while also strengthening the momentum toward the eradication of cancer.

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Mesenchymal stem cells（MSCs） exhibit anti-inflammatory, antioxidant, pro-angiogenic, and anti-fibrotic properties, as well as differentiation potential. MSC has been reported to hold the potential for the treatment of inflammatory diseases and the regeneration of damaged tissue in various organs, including the heart, kidneys, liver, skin and neurons. However, following intravenous administration, only a small percentage of MSCs successfully accumulate in target tissue. The accumulation of MSCs at lesion sites and their interaction with target cells are critical for enhancing therapeutic efficacy. To address this limitation, modifying the surface of MSCs with targeting ligand molecules that specifically bind to proteins expressed on target cells has emerged as an effective strategy. Recently studies have demonstrated the feasibility and efficacy of modifying MSCs with a variety of targeting ligands. These ligands include receptors, adhesion molecules, antibodies, target-specific binding peptide, and aptamers. Currently, four principal methods, （1）pretreatment and preconditioning, （2）Genetic modification, （3）Anchorage via hydrophobic interactions, and （4）Covalent conjugation, are employed to modify the surface of MSCs with targeting ligand molecules. This review provides a comprehensive overview of cell surface modification techniques for MSCs using these methods. In addition, a comparative analysis of these approaches is presented, highlighting their respective characteristics.

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Cardiac diseases are on the increase worldwide, and new treatment approaches that complement existing therapies, such as assisted ventricular assist devices and heart transplants, are being developed. Cell transplantation therapy has gained significant focus as a treatment aimed at regenerating myocardium, and methods using cell sheet technology have progressed from basic research to clinical application. The Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine has been pursuing the clinical application of cell transplantation therapy for heart failure patients, starting with autologous skeletal myoblast cell sheets, followed by iPS cell-derived cardiomyocyte sheets, and then adipose stem cell spray transplantation, which was developed based on cell sheet technology. This report outlines the background and status of the development of myocardial regeneration therapy by cell transplantation in our department.

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The liver is a unique organ with the ability to regenerate, but when it reaches the end stage of chronic liver disease, liver cirrhosis, the liver becomes unable to regenerate due to the fibrosis that has deposited in the liver. Although the radical treatment of decompensated cirrhosis is liver transplantation, due to a shortage of donors, etc., there is widespread development of liver regeneration therapy using mesenchymal stem cells （MSCs）, etc. There have been clinical reports of liver regeneration therapy for liver cirrhosis using autologous bone marrow-derived MSCs, and a certain level of efficacy has been suggested. We have also developed a method to improve the efficacy of liver regeneration therapy for decompensated liver cirrhosis by changing the infusion route of cultured autologous bone marrow-derived MSCs from peripheral vein to hepatic artery, and then we are currently conducting the investigator-initiated trial in our Yamaguchi university hospital.

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Since cells can plastically change their functions through cell fate conversion, controlling cell fate plastically and precisely is important for the efficacy and safety of cell medicines. To achieve this, attempts have rapidly increased in recent years to realize spatiotemporal control and efficacy of treatments by endowing therapeutic cells with a fate conversion switch so that the therapeutic cells can function when and where they are needed. In this article, I would like to review the historical progress of molecular/cellular biology, optogenetics, and synthetic biology, and discuss the current status of design concepts and development of signal inputs and outputs of synthetic receptors, including those developed by the authors, as well as future challenges and prospects.

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Nanozora^Ⓡ（generic name: ozoralizumab（genetic recombination））is a humanized bispecific NANOBODY^Ⓡ compound consisting of two anti-human TNFα NANOBODY^Ⓡ molecules and one anti-human serum albumin NANOBODY^Ⓡ molecule. It bivalently binds to soluble and membrane-bound human TNFα and strongly inhibits the activity of soluble TNFα. Animal studies of ozoralizumab demonstrated an extended plasma half-life by binding to serum albumin, and its rapid transfer into systemic circulation and distribution to inflamed tissues after subcutaneous injection. The efficacy and safety of Nanozora^Ⓡ have been confirmed in clinical trials. Nanozora^Ⓡ 30 mg subcutaneous injection syringe was approved for manufacturing and marketing in September 2022 in Japan, followed by the approval of Nanozora^Ⓡ 30 mg subcutaneous injection auto-injector in July 2023, which is expected to enhance safety and user convenience. This article reviews the structural characteristics of ozoralizumab, preclinical and clinical findings, and the development history of its formulation.

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