Recent progress in regenerative medicine research using iPS cells is noteworthy, which has led to the start of clinical trials of cell therapies for retinal and neurodegenerative disorders. In addition, regenerative medicine research of other organs, such as kidney and pancreas, has also advanced and enabled to generate kidney organoids and pancreatic islet-like structures in vitro. Transplantation experiments using animal disease models have also been vigorously performed to realize cell therapies. In this article, the current status and future perspectives of regenerative medicine using iPS cells against intractable disorders, especially kidney diseases and diabetes, will be summarized.

In July 2010, the Japanese Organ Transplantation Act was revised, but many serious issues of pediatric organ donation remain, and continued action remains essential. This article describes the details of problem in pediatric organ donation and end-of-life care for children. Concrete problems which must be solved are transplant tourism, donor shortage, estimation of child abuse at organ donation, end-of-life care, and so on. Therefore, we must engage in these problems, and it is necessary to deepen discussions on the theme.

Recently in Japan, many organ donors are older in age with complications such as hypertension or diabetes mellitus, thus the decision for renal transplant centers to accept and transplant kidneys from such donors are becoming complex. In this review, we introduce known donor risk factor data linked to post transplant renal dysfunction investigated by the committee established by the Japanese Society for Clinical Renal Transplantation, and also renal graft survival rate data analyzed by the Japan Organ Transplant Network in the Organ Donation and Transplantation Databook 2017. Also, we introduce criteria and risk indexes that are utilized abroad to evaluate the expected function of donor kidneys. Lastly, we report the research project to develop an original index model for the evaluation of the suitability of deceased donor kidneys in Japan.

A physiologically based pharmacokinetic model adapted to the clinical data was constructed in order to evaluate the contribution of liver regeneration as well as hepatic and intestine CYP3A5 genotypes on tacrolimus pharmacokinetics in adult patients after living-donor liver transplantation. As a result, the oral clearance of tacrolimus was affected by the CYP3A5 genotypes in both the liver and intestine to the same extent. Population pharmacokinetic and pharmacodynamic analysis of mycophenolate was performed in 49 patients undergoing hematopoietic stem cell transplantation. Simulations based on the final parameters show that the dosage adjustment based on plasma concentrations of mycophenolate is required especially for patients with renal dysfunction and/or diarrhea. In conclusion, pharmacometrics is a useful methodology for individualized and optimized therapy of immunosuppressants.

Lung transplantation has established for end-stage respiratory failure. The number of lung transplantation is currently increasing in Japan. In terms of procurement of lungs from donor, there are cold ischemic time and warm ischemic time. According to the guideline, total ischemic time, which is both cold and warm ischemic time, should be within 8 hours, because long ischemic time leads to primary graft dysfunction as a cause of death after transplant operation. Actually, the average of total ischemic time was more than 9 hours in our lung transplant program. Therefore, it is necessary for safe lung transplantation to keep donor lung preservation stable for long time. While we take the metabolism during lung preservation into account, donor lungs need glucose and oxygen to produce energy as adenosine tri-phosphate. Glucose would be provided from perfusate which contains rich glucose. Also, oxygen should be supplied from airway. In case of 24 hours lung preservation by conventional preservation method, concentration of oxygen was significantly decreased and carbon dioxide was significantly increased in the airway of isolated lungs in swine. As the reason for that, harvested lungs need oxygen for long-term hypothermic preservation to keep their metabolism. We invented the method of continuous ventilated-lung preservation (CVLP) for the purpose of long-term lung preservation, collaborating with Department of Biomedical Engineering. The container of CVLP consists of a ventilator, ice packs, a circulator and an air filter. And this container can be conveyed by public transportation. When we preserved harvested lungs from swine with CVLP container, the donor lungs were kept well for 24 hours in terms of improving atelectasis in appearance. We hope the new method of hypothermic lung preservation with continuous ventilation contributes to better outcome of lung transplantation in future.

The cell therapy using human pluripotent stem cells (hPSC) technology is expected to overcome the donor shortage problem of heart transplantation, however neither the efficacy nor safety of hPSC-derived cardiomyocytes (CM) has been well established. The transplantation of hPSC-derived CM potentially has some problems; low engraftment efficiency, concern of tumor formation, and arrhythmia associated with immature cells. In order to resolve these problems, we developed the new techniques to purify and culture a large number of CM in vitro and enhance the cell retention rate in vivo. For clinical application to heart failure, the effective and safe transplantation strategy for the engraftment of hiPSC-derived CM must be established.

The wonderful discoveries in basic research are leading to practical use as “Cellular and Tissue-based Products” in Japan. However, in order to safely deliver living cells to the clinical field of medicine, development of transport and preservation technology is essential. In this review, we introduce approved products as an example, show what kind of preservation method is adopted, and report on the verification results of the preservation method of the products currently under development.

In this article, we focus on the kidney regenerative research field and outline the latest research results. We first explain the history of nephron progenitor cells (NPCs) that are the basis of kidney organoid production. Next, we summarize the development of expansion culture method of NPCs derived from mouse embryonic kidney (mNPCs) and human induced pluripotent stem (iPS) cell-derived NPCs (hiPSC-NPCs), and the current status of cell therapies for acute kidney injury (AKI) via paracrine factors secreted by mNPCs and hiPSC-NPCs. Finally, we discuss the future perspectives of cell therapies and other possible applications using hiPSC-NPCs against kidney diseases.

Pluripotent stem cells (PSCs) are expected to be a promising cell source in the field of regenerative medicine and cell-based drug screening because of their high self-renewal capability while preserving pluripotency. To realize these applications, large-scale and efficient cell production methodologies are highly required. In this short review, we introduced typical suspension culture methods with their advantages and disadvantages. In addition, we explained our latest trials concerning pancreatic β cells differentiation of human induced pluripotent stem cells (hiPSCs) using suspension culture system with dialysis operations.

In order to increase organ donation, it is essential to centralize the provision system and reduce the burden on the organ provider side. By providing human and material resources to other hospitals, the organ donor center will reduce the burden on the organ providers and also provide better care for donor families. At the Fujita Medical University, the transplant physicians are in charge of the main department of organ donors after the second legal brain death judgment. Furthermore, the anesthesiologists are involved in respiratory and circulatory management before surgery, resulting in a better organ delivery system. We believe that the reduction of burden on the organ provider side and human and material intensification will lead to more organ donation.

The Japanese Pancreas and Islet Transplantation Association (JPITA) started to prepare for clinical islet transplantation in 1998 and the first islet transplantation was performed in 2004 at Kyoto University. In Era 1, 33 isolated islets from DCD donors were used for islet transplantation to 18 type 1 diabetic patients. 5-year graft survival, however, was poor, that was 22.2% in all patients and 30% in the patients who underwent repeated transplantations. In Era 2, using a newly designed immunosuppressive protocol and the use of DBD donors, two patients out of recent 5 patients have achieved insulin independency. The most important issue of clinical islet transplantation in Japan is to achieve insurance application.

In vivo imaging technology can detect and diagnose a total of transplanted stem cells remains unestablished. In order to enhance the safety and treatment effect of regenerative medicine, it is necessary to understand where transplanted stem cells accumulate in the tissue and how accumulated cells behave in the tissue at a single cell level. In this study, we challenged the innovative diagnosis of transplanted stem cells in acute liver failure model mice by quantum dots (QDs) fluorescence imaging and whole tissue clearing technologies.

After transplantation of stem cells labeled with QDs655 into the living body of the acute liver failure model mice through tail vein, it was confirmed that the transplanted stem cells were mainly accumulated in the lung and liver of the mice using in vivo imaging system. In addition, we succeeded in revealing the spatiotemporal distribution of transplanted stem cells at the single cell level by organ clearing and 3D imaging of organs using light sheet fluorescence microscopy.

Robot-assisted surgery has recently become an important treatment modality in the field of gastrointestinal surgery. However, it is still under development in hepatobiliary and pancreatic surgery probably because of technical difficulty and insufficient appropriate instruments. Nevertheless, functional advantages equipped in the robotic system may compensate for the inherent lacks in conventional laparoscopic liver resection. Particularly, highly complex anatomic liver resection and liver resection with vasculo-biliary reconstruction are expected to be future important targets for robotic liver resection. Herein, we present our experience with 83 cases of robotic liver resection and discuss our surgical results.

The organ viability assessment is important to expand the donor pool using donation after circulatory death (DCD) donor for organ transplantation. In particularly, the liver assessment using machine perfusion (MP) prior to transplantation is necessary to prevent a primary non function and a delayed graft function. In this review, the liver assessment methods using the metabolic index of the organ are introduced and discussed. These techniques can clarify the detail organ viability. Also combination of several assessment methods is important to improve the MP for next generation of transplantation.