Mesenchymal Stem Cells Modulate the Immune System in Developing Therapeutic Interventions

Mesenchymal stem cells (MSCs) are emerging as key players in regenerative medicine for the treatment of various diseases associated with the inflammation and degeneration, thereby aiding in therapeutic advancements. Several tissues have been identified as potential sources of MSCs including the bone marrow, cord blood, dental pulp, umbilical cord, adipose tissue, peripheral blood, and fetal liver, of which some are clinically recognized. MSCs are capable of differentiating into cells of multiple lineages and therefore established as suitable candidates for transplantation in damaged organs. They have added advantage of higher proliferation, easy expansion, and, more importantly, the absence of HLA class II receptors, with potential applications extending toward allogenic settings. MSCs are actively involved in different mechanisms related to repair and regeneration of tissues via immunomodulation, transdifferentiation, paracrine factors, etc. They are known to exhibit profound immunomodulatory effect on T and B cells and natural killer (NK) cells mediated via soluble factors and direct cell-cell contact. The MSCs activate the immune responses and inhibit proliferation, maturation, and differentiation of T and B cells. The MSC-activated immune responses induce the expression of regulatory T cells (Tregs). A plethora of studies have established that MSCs suppress immune responses via immunomodulation that makes them a preferred cell source for the use in clinical trials

3D Culturing of Stem Cells: An Emerging Technique for Advancing Fundamental Research in Regenerative Medicine

Regenerative medicine has been coming into spotlight ever since the realisation that conventional treatments are not enough, and the need for specific therapies has emerged. This, however, has paved way for cell-free therapy using extracellular vesicles. A two-dimensional (2D) cell culture model is widely recognised as the “gold standard” for researching cellular communications ex vivo. Although the 2D culture technique is straightforward and easy to use, it cannot replicate the in vivo ECM interactions & microenvironment. On the contrary, 3D culture culturing technology has emerged which include structures such as spheroids and organoids. Organoids are small replicas of in vivo tissues and organs, which faithfully recreate their structures and functions. These could be used as models to derive stem cells based EVs for manufacturing purposes. The linkages between infection and cancer growth, as well as mutation and carcinogenesis, may be modelled using this bioengineered platform. All in all, 3D culturing derived EVs serves as a novel platform for diagnostics, drug discovery & delivery, and therapy

Mechanisms of Action of Human Mesenchymal Stem Cells in Tissue Repair Regeneration and their Implications

Cell replacement therapy holds a promising future in the treatment of degenerative diseases related to neuronal, cardiac and bone tissues. In such kind of diseases, there is a progressive loss of specific types of cells. Currently the most upcoming and trusted cell candidate is Mesenchymal Stem Cells (MSCs) as these cells are easy to isolate from the tissue, easy to maintain and expand and no ethical concerns are linked. MSCs can be obtained from a number of sources like bone marrow, umbilical cord blood, umbilical cord, dental pulp, adipose tissues, etc. MSCs help in tissue repair and regeneration by various mechanisms of action like cell differentiation, immunomodulation, paracrine effect, etc. The future of regenerative medicine lies in tissue engineering and exploiting various properties to yield maximum output. In the current review article, we have targeted the repair and regeneration mechanisms of MSCs in neurodegenerative diseases, cardiac diseases and those related to bones. Yet there is a lot to understand, discover and then understand again about the molecular mechanisms of MSCs and then applying this knowledge in developing the therapy to get maximum repair and regeneration of concerned tissue and in turn the recovery of the patient

Differentiation Of Mesenchymal Stem Cells (Mscs) To Functional Neuron On Graphene-Polycaprolactone Nanoscaffolds

Spinal cord is an important part of the central nervous system that controls all activities of the body. It is a tubular bundle of nerve fibers and tissues connecting brain to nearly all parts of the body. Nerve cells in an adult human body do not divide and make copies of themselves. Therefore, in case of an injury or damage to any part of spinal cord causes permanent changes to strength, sensation and other body functions. The field of tissue engineering and regenerative medicine which aims to replace and repair damaged tissues, organs or cells entails for effective methods for fabricating biological scaffolds. Here we present synthesis of fibrous scaffolds by a process called electrospinning that can provide a microenvironment in-vitro for differentiation and proliferation of functional neurons from mesenchymal stem cells. These nanofibrous PCL scaffolds with graphene as filler materials are engineered in such a way so as to provide topological, biochemical as well as electrical cues that can enhance neurite extension and penetration. Poly(ε-caprolactone) (PCL) is a FDA approved synthetic biodegradable polyester extensively used in biomedical applications. Graphene, a single layer carbon crystal, based nanomaterials have recently gained considerable interest for tissue engineering applications including osteogenic, neural and differentiation in other lineages due to their favorable chemical, electrical and mechanical properties. Our final aim is that the functional tissues or organs developed in vitro shall be implanted inside body to rehabilitate the biological function that was lost due to injury, abnormality or loss

Mitochondrial dysfunction and its association with age-related disorders

Aging is a complex process that features a functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts aging because mitochondria regulate cellular energy, oxidative balance, and calcium levels. Mitochondrial integrity is maintained by mitophagy, which helps maintain cellular homeostasis, prevents ROS production, and protects against mtDNA damage. However, increased calcium uptake and oxidative stress can disrupt mitochondrial membrane potential and permeability, leading to the apoptotic cascade. This disruption causes increased production of free radicals, leading to oxidative modification and accumulation of mitochondrial DNA mutations, which contribute to cellular dysfunction and aging. Mitochondrial dysfunction, resulting from structural and functional changes, is linked to age-related degenerative diseases. This review focuses on mitochondrial dysfunction, its implications in aging and age-related disorders, and potential anti-aging strategies through targeting mitochondrial dysfunction

Mapping child growth failure across low- and middle-income countries

Child growth failure (CGF), manifested as stunting, wasting, and underweight, is associated with high 5 mortality and increased risks of cognitive, physical, and metabolic impairments. Children in low- and middle-income countries (LMICs) face the highest levels of CGF globally. Here we illustrate national and subnational variation of under-5 CGF indicators across LMICs, providing 2000–2017 annual estimates mapped at a high spatial resolution and aggregated to policy-relevant administrative units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the World Health 10 Organization’s ambitious Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and rates of progress exist across regions, countries, and within countries; our maps identify areas where high prevalence persists even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where subnational disparities exist and the highest-need populations reside, these geospatial estimates can support policy-makers in planning locally 15 tailored interventions and efficient directing of resources to accelerate progress in reducing CGF and its health implications

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Nanotechnology in vaccine and immunology

1135-1143Nanotechnology exploits the exclusive characteristics of nanoparticles with size ranging from 1 to 1000 nanometers (nm). Various nanoparticles have presented magnificent potential for the fabrication of new drug carriers and vaccines. For designing vaccine significant attempts are done to engineer novel vaccines and to increase the efficiency of current vaccines for particular diseases. So far, few vaccines are engineered from killed pathogens or protein sub-units, while various vaccines are founded on live-inactivated pathogens that holds the danger of retrieval of their pathogenicity under some immune-compromised circumstances. To circumvent this designing of risk-free effectual vaccines in combination with satisfactory carrier systems are reflected as a vital requirement to attain preferred humoral and cellular immunity for various diseases. In the past years, utilization of vaccines based on nanoparticle has gained a pronounced responsiveness to increase aimed delivery, immunization approaches and vaccine effectiveness to attain preferred immune retorts at the cell level. To increase vaccine efficiency these nanoparticles mustguard the antigens from early proteolytic disintegration, controlled release, enable antigen internalization and management by antigen presenting cells for harmless human usage. Nanoparticles comprised of polymers, lipids, metals and proteins have previously been exploited to achievefew of these characteristics. In this context, various physicochemical characteristics of nanoparticles have a crucial part in the establishment of vaccine efficiency. This review emphases on the usage of nanoparticles centred vaccine and the importance of characteristics of nanoparticles to achieve effective vaccines delivery in order to prompt preferred host immunity against various diseases