Currently Japan is in a difficult situation where demands of human organs, tissues and cells (collectively human tissues hereafter) for transplantation, for research use and for others including their industrial processing far exceed the small amount of their domestic supply. Analyses show two major causes for this unbalance, i.e., one with many candidate donors losing the chances of donation even with their positive wishes, and the other with the current Japanese law system incapable of coping up with the modern types of demand for human tissues. Here, an ethical and legal solution is proposed to overcome the difficulties. The proposition is composed of five ethical principles and a law with its base on these five principles, as will be referred to as Human Tissue Act of Japan. The first three of the ethical principles, i.e., respect for person, beneficence, and justice, are introduced from Belmont Reports 1978, with a modification of the first for including respect for human tissues in addition, and the third for including equal opportunities for a piece of human tissue to be introduced either into transplantation, research, or industry. The fourth is for those human tissues to be protected as living organisms in a similar manner as described in the Convention of Biological Diversity, 1993, and the fifth for the prohibition of profit-making from unprocessed human tissues, while for the permission of reasonable profit-making when they are processed in the form of commercial products to fulfill social demands. The proposed new law, Human Tissue Act of Japan, if enacted, is expected to be established in order for these five ethical principles to be ensured. In order to bootstrap revising the current Japanese legal framework promptly, the human tissue act of Japan is recommended to be as short and simple as possible.
Human and rodent islets are generally considered to differ in their morphology, composition, signaling molecules, proliferation, and functions. Therefore, the availability of human islets for basic research can improve the understanding of the pathophysiology of diabetes. Islets are used for transplantation to restore beta cell function from diabetes. Although human islet distribution programs for research exist around the world, those availability has been limited in Japan. Here I describe backgrounds and the current status of human islet research. This review also highlights unresolved questions about human islets and proposes future research on human islets in Japan.
Basic and clinical studies for cardiac regenerative medicine is prominently progressing along with the increase of social demands. Regenerative therapy for severe heart failure confers a possibility for the establishment of new therapeutic modalities for pathologies resistant to conventional therapies so far. Already conducted clinical studies using bone marrow-derived stem cells or skeletal myoblasts could not show sufficient therapeutic efficacy as a standardized therapy. Human iPS cell-based cardiac regenerative therapy might realize reconstruction of heart tissue for diseased heart and higher therapeutic efficacy through indirect paracrine factors such as neovascularization by virtue of sufficient preparation of heart-constituent cells without immunological and ethical concerns. In the present review, we introduce current status of stem cell-based cardiac regenerative medicine and future perspectives, especially human iPS cell-derived cardiac tissue which was developed by our research group applying tissue engineering such as cell sheet technology.
Coagulation and complement systems in blood are activated during ischemia-reperfusion injury, resulting in cellular damage and thrombosis. This is one of the important factors which determine graft survival in transplantation of organ and cell. In this paper, I focused on the glycocalyx on endothelial cell surface, which is lost during ischemia-reperfusion injury, and aimed to make the coating sugar materials alternative to the glycocalyx for prevention of coagulation and complement activation. I used polyethylene glycol-conjugated lipid (PEG-lipid) for the cell surface modification and succeeded in the heparinization of the cellular surface. Here I introduced two methods for the heparinization. By using the heparinization methods, it was possible to suppress the coagulation activation in human blood triggered by hMSC, indicating that our heparinization could contribute to the cell protection during ischemia-reperfusion injury in transplantation of organ and cell.
In vivo imaging technology can detect and diagnose almost all of transplanted cells remains unestablished. In order to enhance the safety and treatment effect of regenerative medicine, it is necessary to understand where transplanted cells accumulate in the tissue and how the accumulated cells behave in tissues and organs at a cell level. In this study, we challenged the innovative diagnosis of transplanted islet cells in the liver of mice by advanced technologies such as fluorescence imaging using “quantum dots (QDs)” and whole tissue clearing using “clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC)”. After transplantation of islet cells labeled with QDs800 into the living body of the nude mice through portal vein, it was confirmed that the transplanted islet cells were mainly accumulated in the liver of the mice after 10 min. of transplantation using in vivo imaging system. In addition, we now examine the spatiotemporal distribution of transplanted islet cells at the single cell level by organ clearing and 3D imaging of organs using light sheet fluorescence microscopy.
A machine perfusion technology for transplantation is a promising strategy to preserve organs donated after cardiac death (DCD). Several opportunities to improve and assess the graft viability can be provided during the machine perfusion prior to transplantation. This review introduces an overview of the machine perfusion technology and several assessment methods for liver machine perfusion. Furthermore, innovative liver viability assessment method using imaging measurements defined as “digital biopsy” are introduced to predict graft viability during machine perfusion prior to transplantation. In this study, indocyanine green fluoroscopy image was measured during machine perfusion under normothermic condition. Analysis technique for these images using artificial intelligence to evaluate liver function are proposed.
Organ transplantation is the only definitive treatment for patients suffering end-stage organ failure. However, donor-organ shortage is a severe problem worldwide, and therefore, the development of alternative treatments is urgently needed. The emergence of human induced pluripotent stem cells (hiPSC) is a game-changer for regenerative medicine as it can supply enough cells required for treatment; clinical trials are now conducted in Japan. To generate human tissues from hiPSC for future regenerative medicine, organoid technology offers one of the promising strategies. In this review, we describe the advances in organoid research which we are promoting by utilizing microgravity environment.