Cell sheet technology enables novel approaches to tissue engineering without the use of biodegradable scaffolds. Cell sheet technology consists of a temperature‐responsive culture dish, which enables ...reversible cell adhesion to and detachment from the dish surface by controllable hydrophobicity of the surface. This allows for a non‐invasive harvest of cultured cells as an intact monolayer cell sheet including deposited extra cellular matrices. The monolayer cell sheet can be transplanted to host tissues without using biodegradable scaffolds and sutures. Thick tissue constructs and patterned cell sheets using two or more kinds of cell source are also developed by means of layered cell sheets in vitro. This Progress Report summarizes temperature‐controlled cell adhesion‐detachment behavior and applications of the cell sheet technology to regeneration of cornea, periodontal ligament, bladder epithelia, oesophageal epithelia, myocardium, and liver.
Cell sheet technology utilizing of temperature‐responsive culture dishes has been applied to tissue engineering. Via this technology, cell sheets can be transplanted to host tissues without using biodegradable scaffolds. This Progress Report summarizes temperature‐controlled cell adhesion‐detachment behavior and applications of the cell sheet technology to regeneration of cornea, periodontal ligament, bladder epithelia, oesophageal epithelia, myocardium, and liver.
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Cell sheet technology (CST) is based on the use of thermoresponsive polymers, poly(N‐isopropylacrylamide) (PIPAAm). The surface of PIPAAms is formulated in such a way as to make its typical ...thickness <100 nm. In this review, we first focus on how the methods of PIPAAm‐grafted surface preparations and functionalization are important to be able to harvest a functional cell sheet, to be further transplanted. Then, we present aspects of tissue mimics and three‐dimensional reconstruction of a tissue in vitro. Finally, we give an overview of clinical applications and clinically relevant animal experimentations of the technology, such as cardiomyopathy, visual acuity, periodonty, oesophageal ulcerations and type 1 diabetes.
Mobile health (mHealth) interventions, which require ownership of mobile phones, are being investigated throughout Africa. We estimate the percentage of individuals who own mobile phones in 33 ...African countries, identify a relationship between ownership and proximity to a health clinic (HC), and quantify inequities in ownership. We investigate basic mobile phones (BPs) and smartphones (SPs): SPs can connect to the internet, BPs cannot. We use nationally representative data collected in 2017–2018 from 44,224 individuals in Round 7 of the Afrobarometer surveys. We use Bayesian multilevel logistic regression models for our analyses. We find 82% of individuals in 33 countries own mobile phones: 42% BPs and 40% SPs. Individuals who live close to an HC have higher odds of ownership than those who do not (aOR: 1.31, Bayesian 95% highest posterior density HPD region: 1.24–1.39). Men, compared with women, have over twice the odds of ownership (aOR: 2.37, 95% HPD region: 1.96–2.84). Urban residents, compared with rural residents, have almost three times the odds (aOR: 2.66, 95% HPD region: 2.22–3.18) and, amongst mobile phone owners, nearly three times the odds of owning an SP (aOR: 2.67, 95% HPD region: 2.33–3.10). Ownership increases with age, peaks in 26–40 year olds, then decreases. Individuals under 30 are more likely to own an SP than a BP, older individuals more likely to own a BP than an SP. Probability of ownership decreases with the Lived Poverty Index; however, some of the poorest individuals own SPs. If the digital devices needed for mHealth interventions are not equally available within the population (which we have found is the current situation), rolling out mHealth interventions in Africa is likely to propagate already existing inequities in access to healthcare.
Many healthcare systems in African countries are under-resourced. As a result, people, particularly those living in rural areas, often have to travel large distances to access the medical care they need. Mobile phone-based interventions (also known as mHealth) could make a substantial difference. In Africa, mHealth is already used to diagnose and treat diseases, increase adolescents’ use of sexual and reproductive health services, boost HIV prevention and treatment, and improve maternal and child healthcare.
However, using mHealth services requires owning a basic mobile phone or, in some cases, a smartphone that can access the internet. While mobile phone ownership in Africa is increasing rapidly, data on who has them and what types of phones they have are limited. If geographic, income, or gender-based inequities exist, mHealth interventions may not be able to reach those who would benefit the most.
To close this knowledge gap, Okano et al. analyzed data on the mobile phone ownership of people living in 33 of the 54 countries in Africa. They used mathematical models and data collected from 44,224 people in Afrobarometer, a continent-wide survey conducted between 2017 and 2018. Okano et al. estimated that 80% of African adults in these 33 countries owned a mobile phone, and half of these devices were smartphones.
Although ownership levels varied between the 33 countries, there were substantial inequities that appeared across all of them. More men than women owned a mobile phone. Residents in urban areas and wealthy individuals were also more likely to have a mobile phone than people living in rural areas and poorer individuals, respectively. However, in some countries, the least wealthy were also found to sometimes own smartphones.
Okano et al. also found that people living closer to a health clinic were more likely to have a mobile phone than those living further away. Mobile phone ownership was also higher between 26 to 40 year olds, and then decreased with age. In addition, people under 30 were more likely to have a smartphone, whereas older individuals were more likely to own a mobile phone that does not connect to the internet.
These findings suggest that there are large inequities in mobile phone ownership. If these are not addressed, rolling out mHealth interventions could worsen existing health disparities in African countries. Efforts need to be made across the continent to expand access to phone devices and reduce substantial internet costs. This will ensure that mHealth interventions benefit everyone across Africa, particularly those who need them most.
Twenty-six million people are living with HIV in sub-Saharan Africa; epidemics are widely dispersed, due to high levels of mobility. However, global elimination strategies do not consider mobility. ...We use Call Detail Records from 9 billion calls/texts to model mobility in Namibia; we quantify the epidemic-level impact by using a mathematical framework based on spatial networks. We find complex networks of risk flows dispersed risk countrywide: increasing the risk of acquiring HIV in some areas, decreasing it in others. Overall, 40% of risk was mobility-driven. Networks contained multiple risk hubs. All constituencies (administrative units) imported and exported risk, to varying degrees. A few exported very high levels of risk: their residents infected many residents of other constituencies. Notably, prevalence in the constituency exporting the most risk was below average. Large-scale networks of mobility-driven risk flows underlie generalized HIV epidemics in sub-Saharan Africa. In order to eliminate HIV, it is likely to become increasingly important to implement innovative control strategies that focus on disrupting risk flows.
Summary In high-income countries after World War II, the widespread availability of effective antimicrobial therapy, combined with expanded screening, diagnosis, and treatment programmes, resulted in ...a substantial decline in the incidence of syphilis. However, by the turn of the 21st century, outbreaks of syphilis began to occur in different subpopulations, especially in communities of men who have sex with men. The reasons for these outbreaks include changing sexual and social norms, interactions with increasingly prevalent HIV infection, substance abuse, global travel and migration, and underinvestment in public-health services. Recently, it has been suggested that these outbreaks could be the result of an interaction of the pathogen with natural immunity, and that syphilis epidemics should be expected to intrinsically cycle. We discuss this hypothesis by examining long-term data sets of syphilis. Today, syphilis in western Europe and the USA is characterised by low-level endemicity with concentration among population subgroups with high rates of partner change, poor access to health services, social marginalisation, or low socioeconomic status.
Background: With the recent development of endoscopic submucosal dissection (ESD), large oesophageal cancers can be removed with a single procedure, with few limits on the resectable range. However, ...after aggressive ESD, a major complication that arises is postoperative inflammation and stenosis that can considerably affect the patient’s quality of life. Aims: To examine a novel treatment combining ESD and the endoscopic transplantation of tissue-engineered cell sheets created using autologous oral mucosal epithelial cells, in a clinically relevant large animal model. Methods: Oral mucosal epithelial cells, harvested from beagle dogs, were cultured under normal conditions at 37°C, on temperature-responsive dishes. After ESD (5 cm in length, 180° in range), cell sheets were harvested by a simple reduction in temperature to 20°C, and transplanted by endoscopy. Results: The transplanted cell sheets were able to adhere to and survive on the underlying muscle layers in the ulcer sites, providing an intact, stratified epithelium. Four weeks after surgery, complete wound healing, with no observable stenosis, was seen in the animals receiving autologous cell sheet transplantation. By contrast, noticeable fibrin mesh and host inflammation, consistent with the intermediate stages of wound healing, were observed in the control animals that received only ESD. Conclusions: These findings in a clinically relevant canine model show the effectiveness of a novel combined endoscopic approach for the potential treatment of oesophageal cancers that can effectively enhance wound healing and possibly prevent postoperative oesophageal stenosis.
The majority of people with HIV live in sub-Saharan Africa, where epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, the role of population-level ...mobility in the development of generalized HIV epidemics has not been studied. Here we do so by studying historical migration data from Botswana, which has one of the most severe generalized HIV epidemics worldwide; HIV prevalence was 21% in 2021. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswana’s epidemic, the population was extremely mobile and the country was highly connected by substantial migratory flows. We test this mobility hypothesis by conducting a network analysis using a historical time series (1981–2011) of micro-census data from Botswana. Our results support our hypothesis. We found complex migration networks with very high rates of rural-to-urban, and urban-to-rural, migration: 10% of the population moved annually. Mining towns (where AIDS cases were first reported, and risk behavior was high) were important in-flow and out-flow migration hubs, suggesting that they functioned as ‘core groups’ for HIV transmission and dissemination. Migration networks could have dispersed HIV throughout Botswana and generated the current hyperendemic epidemic.
Over 25 million people in sub-Saharan Africa live with HIV. After reporting its first AIDS case in 1985, Botswana is one of the most severely affected countries in the region, with one in five adults now living with HIV.
Movement of the population is likely to have contributed to a geographically dispersed, and high-prevalence, HIV epidemic in Botswana. Since 1985, urbanization, rapid economic and population growth, and migration have transformed Botswana. Yet, few studies have analyzed the role of population-level movement patterns in the spread of HIV during this time.
By studying micro-census data from Botswana between 1981 and 2011, Song et al. found that the country’s population was highly mobile during this period. Reconstructions of internal migration patterns show very high rates of rural-to-urban and urban-to-rural migration, with 10% of Botswana’s population moving each year. The first reported AIDS cases in Botswana occurred in mining towns and cities where high-risk behavior was prevalent. These areas were also migration hubs during this period and could have contributed to the rapid spread of HIV throughout the country as infected individuals moved back to rural districts.
Understanding human migration patterns and how they affect the spread of infectious diseases using current data could help public health authorities in Botswana and additional sub-Saharan African countries design control strategies for HIV and other important infections that occur in the region.
Summary Background Worldwide, approximately 35 million individuals are infected with HIV; about 25 million of these live in sub-Saharan Africa. WHO proposes using treatment as prevention (TasP) to ...eliminate HIV. Treatment suppresses viral load, decreasing the probability an individual transmits HIV. The elimination threshold is one new HIV infection per 1000 individuals. Here, we test the hypothesis that TasP can substantially reduce epidemics and eliminate HIV. We estimate the impact of TasP, between 1996 and 2013, on the Danish HIV epidemic in men who have sex with men (MSM), an epidemic UNAIDS has identified as a priority for elimination. Methods We use a CD4-staged Bayesian back-calculation approach to estimate incidence, and the hidden epidemic (the number of HIV-infected undiagnosed MSM). To develop the back-calculation model, we use data from an ongoing nationwide population-based study: the Danish HIV Cohort Study. Findings Incidence, and the hidden epidemic, decreased substantially after treatment was introduced in 1996. By 2013, incidence was close to the elimination threshold: 1·4 (median, 95% Bayesian credible interval BCI 0·4–2·1) new HIV infections per 1000 MSM and there were only 617 (264–858) undiagnosed MSM. Decreasing incidence and increasing treatment coverage were highly correlated; a treatment threshold effect was apparent. Interpretation Our study is the first to show that TasP can substantially reduce a country's HIV epidemic, and bring it close to elimination. However, we have shown the effectiveness of TasP under optimal conditions: very high treatment coverage, and exceptionally high (98%) viral suppression rate. Unless these extremely challenging conditions can be met in sub-Saharan Africa, the WHO's global elimination strategy is unlikely to succeed. Funding National Institute of Allergy and Infectious Diseases.
STUDY QUESTION
Can regenerative-medicine techniques using oral mucosal epithelial cell sheets (OMECS) provide a new treatment method for intrauterine adhesions (IUA) which cause female infertility?
...SUMMARY ANSWER
Transplantation of OMECS was confirmed to be effective in preventing IUA after endometrial damage in rats.
WHAT IS KNOWN ALREADY
Uterine disorders such as IUA, commonly known as Asherman's syndrome, are one factor that can result in infertility. Clinical therapy for this kind of disease is targeted at the prevention of re-adhesion by surgical synechiotomy, administration of hormones after the operation, and the use of intrauterine devices. Recently, a new approach called ‘cell-sheet engineering’, which harvests confluent culture cells as a contiguous cell sheet having intact cell–cell junctions and an extracellular matrix, without having to use enzymatic treatment, has been developed for tissue regeneration.
STUDY DESIGN, SIZE, DURATION
OMECS were prepared from rat oral mucosal tissues. An IUA model was made in rat uteri, and OMECS were transplanted into the model. Uteri transplanted with OMECS were compared with the non-transplanted control uteri by histological analysis at 1, 2 and 8 days after surgery (n = 3).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Oral mucosal tissues were resected from neonatal rats, and oral mucosal epithelial cells were collected with enzymatic treatment. An isolated cell suspension was seeded on a temperature-responsive cell culture-insert and incubated. After being detached from the insert, a cell sheet was transplanted onto the endometrium defect. At 1, 2 and 8 days after surgery, uteri were resected and examined.
MAIN RESULTS AND THE ROLE OF CHANCE
Histological examination of the non-treated specimens at 1, 2 and 8 days after surgery did not show any uterine cavities typically caused by IUA. In contrast, the histology of uteri transplanted with OMECS immediately after endometrial damage showed the presence of uterine cavities, and furthermore, stratified squamous epithelial cells on the luminal surface (n = 3).
LIMITATIONS, REASONS FOR CAUTION
The results of this study are difficult to apply directly to humans, because the structure and function of rat uteri are different from those of human.
WIDER IMPLICATIONS OF THE FINDINGS
Transplantation of OMECS offers a reliable method not only to protect the woman's fertility from intrauterine re-adhesion after synechiotomy for IUA or uterine lumen adhesion but also to prevent adhesion after any intrauterine surgery in clinical cases.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems ‘Cell Sheet Tissue Engineering Center (CSTEC)’ from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. Teruo Okano is a director on the board of CellSeed Inc. Tatsuya Shimizu had been a scientific consultant for CellSeed Inc. until December 2013. These two authors are stakeholders of the company and are inventors of cell sheet-related patents. Tokyo Women's Medical University is receiving research funds from CellSeed Inc. The other authors have no conflicting interests to declare.
TRIAL REGISTRATION NUMBER
Not applicable.
Summary
We examined the effectiveness of coordinators’ interventions to prevent secondary fractures in patients with fragility fractures. These coordinator-based interventions improved bone density ...assessment implementation and treatment rates, and enhanced treatment persistence rates in the early stages following fractures.
Introduction
This study aimed to determine the efficiency of coordinator-based osteoporosis intervention in fragility fracture patients during a 2-year period.
Methods
A prospective intervention randomized control study was conducted at seven medical facilities from January 2015 to March 2017. Postmenopausal women and men over 50 years old with fragility fractures were randomly divided into the coordinator intervention (LI; 70 patients) and without intervention (non-LI; 71 patients) groups. The osteoporosis treatment rate, osteoporosis treatment persistence rate, fall rate, fracture incidence rate, and bone density measurement rate 3 months, 6 months, 1 year, and 2 years after registration were compared between the two groups. Non-parametric tests were used to analyze data at each inspection period.
Results
The osteoporosis treatment initiation rate was significantly higher in the LI group than in the non-LI group (85.7% vs. 71.8%;
p
= 0.04). The LI group had significantly higher bone density assessment implementation rates than the non-LI group at the time of registration (90.0% vs. 69.0%;
p
= 0.00) and 6 months after registration (50.0% vs. 29.6%;
p
= 0.01), but not 1 or 2 years after registration. In addition, no significant differences in fall or fracture incidence rates were found between the two groups.
Conclusion
The coordinator-based interventions for fragility fractures improved bone density assessment implementation and treatment rates and enhanced treatment persistence rates in the early stages following bone fractures. The findings suggest that liaison intervention may help both fracture and osteoporosis physicians for the evaluation of osteoporosis and initiation and continuation of osteoporosis medication.
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