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Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV‐associated cervical lesions is HPV genotype‐dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high‐risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high‐risk HPVs, HPV18 has some peculiar characteristics different from those of other high‐risk HPV types; the detection rate in precancerous lesions is much lower than those of other high‐risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell‐like cells. In this context, this review outlines the natural history of HPV‐infected cervical lesions and the characteristics of each HPV genotype. [ABSTRACT FROM AUTHOR]

The Bioethics Act in the Republic of Korea has undergone great fluctuations akin to the pendulum of a clock. Since Professor Hwang's research ethics issue, domestic embryonic stem cell research has lost its vitality. This study argues that the Republic of Korea needs a reference point that does not waiver. This study examined the characteristics of life science- and ethics-related systems in the Republic of Korea and Japan. It also examined the pendulum-like policy changes in the Republic of Korea. It then compared the strengths and weaknesses between the Republic of Korea and Japan. Finally, we proposed a system improvement strategy for the development of bioethics research in Asian countries. In particular, this study argues that the advantages of Japan's slow but stable system should be introduced. [ABSTRACT FROM AUTHOR]

The first product in the world for ex vivo cultivated oral mucosal epithelial cell transplantation (COMET) to treat limbal stem cell deficiency (LSCD), named Ocural®, was launched in June 2021 in Japan. COMET was performed on two patients, including the first case in the post-marketing phase of Ocural®. Pathological and immunohistochemical examinations were also carried out using specimens obtained before and after COMET and the spare cell sheet. In case 1, the ocular surface remained free from epithelial defects for approximately six months. In case 2, although defect of the cornea-like epithelia was observed after COMET for one month, it was resolved after the insertion of lacrimal punctal plugs. In case 1, adjuvant treatment was interrupted due to an accident during the second month after COMET, resulting in conjunctival ingrowth and corneal opacity. Eventually, a lamellar keratoplasty was required at six months after COMET. Immunohistochemistry revealed the presence of markers for stem cells (p63, p75), proliferation (Ki-67), and differentiation (Keratin-3, -4, and -13) in both the cornea-like tissue after COMET and a cultivated oral mucosal epithelial cell sheet. In conclusion, Ocural® can be accomplished without major complications, and the stem cells derived from oral mucosa might be successfully engrafted. [ABSTRACT FROM AUTHOR]

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retinal, cardiac, and dopamine-producing cells differentiated from human induced pluripotent stem (iPS) cells and hepatocyte-like cells differentiated from human embryonic stem (ES) cells. The distinctive feature of the stem cell research in Japan is the use of iPS cells. A national framework was also been set-up to attain the final goal: health insurance coverage. Now, insurance covers cell transplantation therapies for the repair and recovery of damaged skin, articular cartilage, and stroke as well as therapies introduced from abroad, such as allogeneic mesenchymal stem cells for graft-versus-host disease and chimeric antigen receptor-T (CAR-T) cell therapy. To prepare this review, original information was sought from Japanese authentic websites, which are reliable but a little hard to access due to the fact of multiple less-organized databases and the language barrier. Then, each fact was corroborated by citing its English version or publication in international journals as much as possible. This review provides a summary of progress over the past decade under the national program and a state-of-the-art factual view of research activities, government policy, and regulation in Japan for the realization of stem cell therapy. [ABSTRACT FROM AUTHOR]

Policy focus gives scientists an incentive to pursue specific research subjects and influences a trend of scientific research. This study examines how public grant is allocated for stem cell research in Japan and shows that scientists are likely to advance their research toward the direction led by policy. Since Japanese scientists discovered a method to generate induced pluripotent stem cell (iPSC) in 2006, public financial and institutional support has skewed toward iPSC. The 2012 Nobel Prize in Physiology or Medicine for iPSC has also had an impact on policy and scientists' selection of stem cells. Scientists in the top universities are likely to select iPSC research. In addition, iPSC research obtains more amount of public grant funding than other stem cell research. However, scientists' age has no relevant impact on selecting iPSC research. Finally, this study concludes that targeted public funding skews knowledge portfolio by scientists in a nascent field. [ABSTRACT FROM AUTHOR]

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Background: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined.Methods: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 -/- mice.Results: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/- tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 -/- mice than in WT mice.Conclusions: ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a "premature lung aging" effect. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells (HSCs) for autologous transplantation in Japanese patients with multiple myeloma (MM). In a randomized study, patients received G-CSF (filgrastim, 400 µg/m 2 /day) for 4 days prior to the first dose of plerixafor. Starting on Day 4 evening and for up to 4 days, patients received either plerixafor (240 µg/kg/day) + G-CSF group (PG group) or G-CSF alone (G group). Daily apheresis started on Day 5 for up to 4 days, or until ≥6 × 10 6 CD34+ cells/kg were collected. A total of 7 patients were randomized in each treatment group. Five patients in PG group and no patients in G group achieved a collection of ≥6 × 10 6 CD34+ cells/kg in ≤2 days of apheresis [difference of 71.4% (90%CI 29-100%)]. These results were supported by the shorter median time to collect ≥6 × 10 6 CD34+ cells/kg (2 days in PG group; no patient in G group). The incidence of treatment emergent adverse events (TEAEs) was higher in PG group than in G group. Plerixafor was well tolerated, and effective for the mobilization/collection of peripheral HSCs for autologous transplantation in Japanese patients with MM.

This article describes a recent trend in Japanese research, development and commercialization toward the application of stem cell technologies. Japan is the world's third largest economy and has a significant national presence in the pharmaceutical and biotechnology businesses; as such, stem cell R&D is abundant in the country. As indicated by the second largest share of patent applications worldwide, Japan had been expected to assert significant added value in the commercialization and industrial application of stem cell technologies; however, difficulties have impeded clinical development in this area, particularly the very small number of clinical trials and approved products for regenerative medicine or cell therapy. To address this 'Japan paradox', this report provides an overview of approaches for the commercialization of stem cell technologies in areas such as drug discovery, cell therapy and regenerative medicine, by discussing representative case examples of listed firms.