The reason stem cells are so interesting to researchers is that stem cells

Stem cell research that is publicly funded and conducted under established standards of open scientific exchange, peer review, and public oversight offers the most efficient and responsible means of fulfilling the promise Sep 11, 2023 · Framing the Issue. There are even stem cells that Apr 7, 2023 · Stem cells have been the subject of research for years due to their enormous therapeutic potential. Embryonic stem cells, by contrast, can divide almost indefinitely and can give rise to every cell type in the body, suggesting that they may be the most versatile source of cells for research and transplantation therapy. Stem cells possess the unique characteristic of being able to develop into different specialized cells such as nerve cells, muscle cells, and blood cells. During the process, the nucleus of a human egg cell is removed and replaced with the nucleus of a donor’s adult cell, which contains the person’s DNA. Encouragingly, as of December 2019, there are 791 clinical trials underway using Jul 17, 2008 · The SCNT process was developed by the Scottish scientist Ian Wilmut, who cloned Dolly the sheep in 1996. There Are More Than Adult and Embryonic Stem Cells That Researchers Are Looking At Today. . Although the CSC hypothesis is debated by cancer researchers, it still receives ongoing, increasing interest in the scientific community. iPSCs and other highly multipotent stem cells have many additional important uses Feb 21, 2019 · Abstract. This review looks back at some of the key developments in stem cell research as well as the evolution of the ISSCR as part of that field. There are several different types of stem cells produced and maintained in our system throughout life. It proposes that the growth and progression of numerous cancers are driven by small subpopulations of stem-like cells with self Jun 6, 2020 · Communicating Impactful Stem Cell Research. Jan 2, 2024 · Stem cells grown in the laboratory, or adult cells reprogrammed to be stem cells, might have genetic damage. In the end, however, more people have been helped by stem cells than hurt by it and the practice has saved numerous lives. With the increased risk of organ failure and neurodegenerative disease associated with our ability Jul 7, 2014 · Some applications of stem cell research, such as disease modeling, drug discovery and testing, cell line banking, and commercialization of stem cell therapies, also give rise to ethical considerations specific to the field [11, 12, 14, 16, 24–26, 28, 29]. There are three main sources of human embryonic stem cell lines. Being fruitful, they multiply into a ball of many cells, a shimmering sphere of human Feb 12, 2019 · For that reason, it is critically important for scientists to actively participate in decisions about funding levels and the development of rules and ethical standards for research using animals, human subjects, stem cells, fetal tissue, and other issues. Other research in Aug 26, 2005 · Figure 1. Feb 26, 2019 · In recent years, stem cell therapy has become a very promising and advanced scientific research topic. Stem cells can theoretically induce, differentiate, and grow into any kind of human cell, tissue, or organ under artificial conditions through histological engineering techniques. Plant Stem Cells and Their Niches. The reason stem cells are so interesting to researchers i that stem cells _____. 1). (A) In the Arabidopsis root, stem cells for all cell types surround the quiescent center (QC), a small group of organizer cells that are required for stem cell maintenance. By. Researchers are looking for other ways to use stem cells in medical therapies. In theory, if stem cells can be grown and their development directed in culture, it would be possible to grow cells of medical importance such as bone marrow, neural tissue or muscle. Figure 1. Being fruitful, they multiply into a ball of many cells, a shimmering sphere of human Sep 29, 2021 · Stem cells: highlights from research. 3. Stem cells are a type of primitive cells Replacing diseased cells with healthy cells, a process called cell therapy, is a promising use of stem cells in the treatment of disease; this is similar to organ transplantation only the treatment consists of transplanting cells instead of organs. Embryonic stem cells might not function in a person's body, and in these cases, the Successful induction of somatic cells into iPSCs represents a milestone in the field of stem cell and regeneration research. Skin grown in culture from just a few skin stem cells can be used to treat burn The use of stem cells in medical treatments already is yielding exciting results and may yield greater medical advances in the future. Stem cells undergo asymmetric cell divisions and their daughter cells differentiate into all root cell types. Researchers believe these so-called induced pluripotent Sep 1, 2017 · The ethical, social and public concerns raised by stem cell interventions have prompted the International Society of Stem Cell Research (ISSCR), an international non-profit organization of stem cell scientists, to issue the Guidelines for stem cell research and clinical translation. Researchers use these cells to study development and disease and, hopefully, to find treatments Apr 4, 2022 · Stem cell (SC) therapies have broad application prospects in the field of regenerative medicine due to the inherent biological characteristics of SCs, such as their plasticity, self-renewal, and multidirectional differentiation potential. Jun 14, 2007 · In 2007, multiple researchers reported that both mouse and human cells could be converted to cells that behave like embryonic stem cells. 5. a. Aug 6, 2022 · The isolations of “mesenchymal stem cells” in 1991 following by the discovery of human pluripotent stem cells have recently contributed to the progress of stem cell-based therapy in the treatment of human diseases. In adult vertebrates, for example, stem cells are typically limited to the production of cell types within one organ or tissue. Over recent decades, they have been studied and utilized for repair and regenerative medicine. , ectoderm, mesoderm, and endoderm) as well as germ One cell line can supply lots of researchers with huge numbers of cells. Research using stem cells that are derived from human embryos has been hotly debated ever since scientists first established human embryonic-stem-cell lines in Oct 22, 2021 · The new guidelines propose three categories of oversight for stem-cell and embryo research (Supplementary Table 1 ): (1) exempt from review by a specialized oversight process, (2) review by a Jan 1, 2019 · Abstract. These stem cells appear to provide an accurate paradigm model system to study tissue-specific stem cells, and they have potential in regenerative Nov 14, 2012 · We begin with a necessarily brief overview of stem cell research. Adult stem cells start out as embryonic stem cells, then become fetal stem cells, and mature into adult Feb 10, 2020 · Researchers are trying to develop stem cell therapies for the future of medicine with the support, caution, and interest of the general public. (1) Human pluripotent stem cells The Stem Cell Divide. Sep 12, 2023 · This article highlights a recent document developed by the International Society for Stem Cell Research (ISSCR) that provides recommendations, including reporting criteria, for scientists using human stem cells in basic research laboratories. Stem cells are noted for their ability to self-renew and differentiate into a variety of cell types. Studying stem cells will help us to understand how stem cells transform into the array of specialized cells that make up the human body. Stem cells are the only cells in your body that make different cell types, like blood, bone and muscle cells. By Rick Weiss. Currently, researchers are investigating the use of adult, fetal and embryonic stem cells as a Jun 17, 2021 · These cells are called cancer stem cells (CSCs) or tumor-initiating cells (TICs). Spare embryos left over from fertility treatment. Stem cells are an ongoing source of the differentiated cells that make up the tissues and organs of animals and plants. Important discoveries from stem cell research are described, and how the improved understanding of basic stem Aug 30, 2023 · A consequence of this is a lack of common understanding of the underlying biology of pluripotent stem cells and their limitations. While Robert Hooke first discovered the concept of cells themselves, the discovery of stem cells is usually credited to Drs. By definition, stem cells are able to divide and make copies of themselves indefinitely (self-renewal). S. Nov 21, 2019 · Induced pluripotent stem cells (iPSCs) are artificial stem cells produced from somatic cells through co-expression of defined pluripotency-associated factors [1, 2]. 00:00. Stem cells are unspecialized cells that can self-renew indefinitely and also differentiate into more mature cells with specialized functions. 2002 Act ensuring the protection of embryos in connection with the importation and use of So, then, the daughter cell can go on to become more specialized while the mother cell replaces the stem cell that divided, initially. A stem cell is a cell with the potential to form many of the different cell types found in the body. Stem cells have two essential properties: (1) They divide to give rise to another stem cell (self-renewal) and, (2) they undergo differentiation to form diverse cell types ( Figure 1A ). Limited access to human material, particularly during early development, has restricted researchers to only scratching the surface of this inherently challenging subject. Pluripotent stem cells are an excellent source of many types of differentiated cells that can be used in regenerative medicine. create a great deal of controversy d. Basic Questions. Medical researchers believe stem cells also have the potential to treat many other diseases. It all started in 1908, when a histologist Alexander Maksimov coined the name stem cells. This article will cover stem cells, which conditions they treat, and their safety. In normal embryonic development, they disappear after the 7th day, and begin to form the three embryonic tissue layers. For several hundred years, researchers have known that the human body is comprised of trillions of tiny Aug 2, 2023 · Stem cell therapy is a type of regenerative medicine used to treat and study disease. Most of the cells in an adult body are “differentiated,” which means that they are committed to being one kind of cell, such as a skin cell or a fat cell. Only after collecting and culturing tissues is it possible to classify cells according to this operational concept. In the medical field, they are used to detect birth defects and used in tissue regeneration as well as in transplantation therapies such as bone marrow transplantation. Major breakthroughs in stem cell research have not yet enjoyed clinical success—all stem cell therapies bar hematopoietic stem cell transplantations remain experimental. 2). Many key scientists have noted the potential in researching stem cells in the following the years after. Literature highlights the significance of understanding stem cell therapy and research to support the development of regenerative medicine [1–3]. Aug 25, 2022 · Stem cells are types of cells that have unique ability to self-renew and to differentiate into more than one cell lineage. They also repair damaged tissue. In addition, public funding offers greater opportunities for regulatory oversight and public scrutiny of stem cell research. b Schematic of the different cell sources that can be used in stem cell-based therapy. Depending on the circumstances and life cycle stages, these cells have different properties and functions. Oct 13, 2021 · The stem cells within the skin are usually named after the niche in which they reside in, i. ESCs extracted from the inner cell mass during the blastocyst stage, however, can be cultured in Abstract. Self-organizing models of the early heart, why dead cells can be therapeutic, and other studies. are not yet specialized for a specific function c. Jan 1, 2023 · Stem cells are currently the ideal seeding cells for tissue engineering (Fig. Why are doctors and scientists so excited about stem cells? Stem cells have potential in many different areas of health and medical research. Underneath the skin, the muscle that contracts to create goosebumps is necessary to bridge the sympathetic nerve’s connection to hair Feb 12, 2019 · For that reason, it is critically important for scientists to actively participate in decisions about funding levels and the development of rules and ethical standards for research using animals, human subjects, stem cells, fetal tissue, and other issues. 2018). Synthetic embryos have been shown to implant into the mouse uterus, though their potential to develop to term has not been demonstrated. They are able to give rise to all the cells in an embryo proper, but not to extra-embryonic tissues, such as the placenta. Further research on stem cell regeneration would be beneficial to those who have Parkinson’s disease, Alzheimer’s disease, heart disease, stroke, burns, cancer, etc. Stem cell research that is publicly funded and conducted under established standards of open scientific exchange, peer review, and public oversight offers the most efficient and responsible means of fulfilling the promise Jun 14, 2007 · Metrics. Feb 14, 2023 · Since stem cells were first discovered, researchers have identified distinct stem cell populations in different organs and with various functions, converging on the unique abilities of self Over the past decade, stem cell research has become the most visible and contentious manifestation of the promise of biological science, akin to the Human Genome Project in the 1990s or recombinant DNA research and biotechnology in the 1970s and 1980s. This manuscript reviews the causes of human aging, the Feb 10, 2020 · Researchers are trying to develop stem cell therapies for the future of medicine with the support, caution, and interest of the general public. Stem cells play a central role both during development and in the adult. Future regulations of embryonic-stem-cell research will be influenced more by economic interests and cultural history than by ethical concerns. We will first introduce a few general concepts and note previous debates that were important in stem cell research but have now Jul 22, 2013 · Stem cells come in two forms, adult and embryonic. It might take only a few mutations for one cell to lose control over its self-renewal and growth and become the source of cancer. Takahashi and Yamanaka (2006) successfully achieved the induction of pluripotent stem cells from mouse embryonic and adult fibroblasts by introducing four factors (Oct3/4, Sox2, c-Myc, and Klf4) under ESC culture conditions. …. This, together with a common failure to fully report on the In her second talk, Fuchs focuses primarily on studies of adult skin stem cells. James Till & Ernset McCulloch. McLaren reported that there are millions of individuals suffering from and succumbing to “incurable degenerative diseases of the nervous system, heart, liver, pancreas, and other organs” annually []. Jul 20, 2020 · In a new study, Harvard University scientists have discovered the reason: the cell types that cause goosebumps are also important for regulating the stem cells that regenerate the hair follicle and hair. May 7, 2021 · A stem cell, found in embryos (embryonic stem cell) and adults (somatic stem cell), is an immature, non-specialized cell that can differentiate into one or more specific functioning or regenerating cell types. Jun 17, 2019 · Therapy-induced cell loss is compensated by haematopoietic stem cells (HSCs), which repopulate the host bone marrow and regenerate the entire haematopoietic system. This makes them of use in the treatment of degenerating diseases. Thus, SCs could delay or even reverse aging. Embryonic stem cells (ESCs) are found in the inner cell mass of the human blastocyst, an early stage of the developing embryo lasting from the 4th to 7th day after fertilization. A totipotent stem cell can become any cell type within the organism in Jun 5, 2024 · The controversy surrounding stem cell research primarily stems from ethical and political concerns. Jun 5, 2023 · Stem cells are typically the source of differentiated cells, but the range of cell types that they can generate differs between species and between stem cells within a species. Therefore new therapies are sought in which autologous stem cells are used Jul 17, 2008 · At the same time, many scientists say that embryonic stem cell research is necessary to unlock the promise of stem cell therapies since embryonic stem cells can develop into any cell type in the human body. Some stem cells, described as totipotent cells, have tremendous capacity to self-renew and differentiate. Important discoveries from stem cell research are described, and how the improved understanding of basic stem May 12, 2020 · Background. The other mechanism is called stochastic differentiation. It is used in cancer treatment and to reduce the risk of infection. Stem cells are undifferentiated cells that have the capacity to renew themselves and to specialize into various cell types, such as blood, muscle, and nerve cells. Bethesda, MD: National Institutes of Health, U. Follicle structures, including oocytes The reason stem cells are so interesting to researchers is that stem cells _____ are not yet specialized for a specific function Although alcohol does not actually kill brain cells, it does cause brain shrinkage and can destory Dec 30, 2020 · Scientists use embryonic stem cells to determine how specific cells can be used to regenerate and repair diseased or damaged tissues in people. Research on human embryonic stem cells, however, is controversial, given the Mar 16, 2015 · Due to their promise for research and health treatments, stem cells have garnered scientific excitement for decades. In a new study, published recently in Stem cell basics. Department of Health and Human Services, 2016 [cited February 1, 2021] Available at Clinical Trial . So, if one stem cell happens to differentiate into two daughter cells instead of a mother and a daughter, another stem cell will notice this and makes up May 27, 2021 · The updated Guidelines for Stem Cell Research and Clinical Translation describe the ethical principles and best practices for basic, translational, and clinical research involving stem cells and human embryos. Whereas adult stem cells, which are found in particular organs of the mature body — the bone marrow, for example, or the brain — can only produce the specialized cells for that particular tissue type, embryonic stem cells derive from a far earlier point in development and thus have the potential to differentiate into every type of cell in Jun 7, 2024 · stem cell, an undifferentiated cell that can divide to produce some offspring cells that continue as stem cells and some cells that are destined to differentiate (become specialized). Encouragingly, as of December 2019, there are 791 clinical trials underway using Jan 27, 2022 · The cancer stem cell (CSC) model, also called the deterministic model, emerged in the late 1990s when researchers began to address the possible relationship between hematopoietic stem cells and human leukemia [9,10]. Who discovered stem cells is a question worthy of exploration. Most neurological diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are incurable or very difficult to treat. The advantage of therapeutic cloning over ESCs is that SCNT stem cells, like iPSCs, are genetically identical to Embryonic stem cells are of great interest to medicine and science because of their ability to develop into virtually any other cell made by the human body. In late 2007, researchers in the United States and Japan succeeded in reprogramming adult skin cells to act like embryonic stem cells. In Stem Cell Information [World Wide Web site]. Most commonly, this controversy focuses on embryonic stem cells. These cells have the ability to renew and differentiate themselves into a wide range of cell types. The egg is then stimulated to begin subdividing, eventually growing into an embryo Jan 29, 2019 · However, when pluripotent SCNT stem cells are harvested from the reconstructed SCNT embryo, the process is called therapeutic cloning, aiming at deriving pluripotent stem cells for future cell therapy and research purposes (Fig. have highly specialized functions Mar 30, 2011 · Glyn Stacey, head of the UK Stem Cell Bank, lists the research community's shift toward serum-free media as one of the most important improvements to stem cell culture in recent years, but plenty Nov 19, 2018 · To fully explore the potential of these versatile cells, NIDCR supports a range of scientists who are working to better understand dental stem cells and their therapeutic promise. Research with embryonic stem cells has enabled Stem-cell research: the state of the art. The development of treatment methods has evoked great expectations. In turn, under certain physiological conditions, they give rise to different cell types (differentiation). For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using Feb 26, 2019 · Haematopoietic stem cells are important because they are by far the most thoroughly characterized tissue-specific stem cell; after all, they have been experimentally studied for more than 50 years. Stem Cell Reports, the ISSCR’s open-access, online journal, has continued to publish impactful stem cell research while serving the stem cell community. 7 While such voluntary guidelines are useful, they lack the Apr 14, 2009 · The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. 30 min read. Now, stem cells are essential blood cancer and blood disorder treatments. This incredible versatility makes them invaluable in medical research and potential treatments. Like embryonic stem cells (ESCs), they can typically proliferate and self-renew indefinitely in vitro and differentiate into derivatives of all three primary germ layers (i. The idea that the remnants of our embryonic past could lead to our demise through cancer is 4 days ago · Definition. Embryonic stem cells, derived from five-day-old embryos, eventually give rise to all the different cells and organ systems of the embryo. This difficulty in identifying stem cells in situ, without any manipulation, limits the Dec 4, 2014 · The Central Ethics Committee for Stem Cell Research (2002) Reviews and evaluates applications for import and use of hESCs as required by the Stem Cell Act. , hair follicle stem cells (HFSCs), melanocyte stem cells (MeSCs), interfollicular epidermis stem cells (IFESCs), and dermal stem cells (DSCs). Embryonic stem cells have the potential to form a complete individual, whereas adult stem cells can only form The Stem Cell Divide. The understanding of human biology and how it relates to that of other species represents an ancient quest. Embryonic stem cells can, in theory, produce any type of tissue in large quantities. Cell lines that already exist. One area of inquiry addresses a needle-in-the-haystack issue: sorting out the relatively scarce stem cells from the other cell types in dental tissue. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of Aug 15, 2011 · Abstract. The updated Guidelines include new recommendations to address the recent scientific advances involving embryos, stem cell-based embryo models, chimeras, organoids, and genome editing. Recent research has shown that the most effective system of repair of the human body is represented by stem cells. The term “stem cells”—shorthand for the controversial type, human embryonic stem cells—is now widely recognized, and it represents a Stem Cells. One of the main issues is the derivation of pluripotent stem cell lines from oocytes and embryos, which raises disputes about the onset of human personhood. Stem cells, on the other hand, are a sort of “blank slate” capable Mar 16, 2015 · The blastocyst is a structure comprising about 300 cells that contains two main regions: the inner cell mass (ICM) and the trophoblast. Issues a written opinion on each application to the licensing authority—the Robert Koch Institute. The first patients were treated Oct 19, 2018 · In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair. Stem cells are defined as precursor cells that have the capacity to self-renew and to generate multiple mature cell types. Stem cells are present inside different types of The stem cell controversy concerns the ethics of research involving the development and use of human embryos. Stem cell therapies have tremendous potential to improve and save lives, but must be vetted through clinical trials . At a recent event hosted by Rush University Medical Center, experts at Rush discussed the role of stem cells in neurosurgery, orthopedics, pediatrics and oncology and how their breakthrough research may Dec 19, 2007 · Adult stem cells are the reserve supply of cells that can multiply when needed for repair of adult organs and tissues. The ICM is made of embryonic stem cells (ES cells), which are referred to as pluripotent. Embryonic stem cells have pluripotent capacity, able to form tissues of all 3 germ layers but unable to form an entire live being. Jan 16, 2017 · How important is the new strategy to reprogram adult cells back, but not all the way back to stem-cell stage — more to a state that is still somehow specific to the organ the cells came from? Mar 30, 2020 · All living things, including humans, are made of cells. Regardless of their niche, these cells are collectively known as skin stem cells (SSCs) ( Figure 1 ). Adult stem cells have the ability to make more stem cells and to generate the cells of a differentiated tissue. In the beginning, one cell becomes two, and two become four. Jun 6, 2022 · The International Society for Stem Cell Research (ISSCR) celebrates its 20 th anniversary in 2022. are created by genetic engineering b. Custom-made embryos created by somatic cell nuclear transfer (SCNT), the technique used to create the sheep Dolly. May 14, 2023 · The Answers Revealed. There is great interest in stem cells The International Society for Stem Cell Research (ISSCR) celebrates its 20 th anniversary in 2022. To date public policy in the United States has attempted to skirt the ethical and These stem cells sometimes cause negative interactions because people are unique creatures and even exact matches don’t always take. A brief history is provided of the derivation of embryonic stem cells from different sources, the challenges of their maintenance, and the evolution of cell culture systems, as well as general guidelines for Page citation: NIH Stem Cell Information Home Page. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. 16, 17, 18 With the increasing maturity of stem cell transplantation technology, the use of stem cells in vivo will surely advance Sep 12, 2023 · Stem cells have the remarkable ability to differentiate into various cell types in the body. Not all stem cell research involves human embryos. Stem cells are unspecialized cells that have not yet “decided” what type of adult cell they will be. Each tissue and organ of the body contains cells that are specialized to perform specific jobs–the liver contains liver cells, the brain contains neurons, the eyes contain light-detecting cells, and so on. C rafting morally sound policies for stem cell research requires at least three kinds of scientific knowledge: first, an account of the medical treatments that stem cell research might make possible — along with an account of the likely challenges facing this research — so that we might judge whether funding such research is in the public interest; second, an understanding of biology and Sep 15, 2021 · Stem cells have been researched for over 100 years. But all human life begins with the encounter between two cells: the sperm cell from the father and the egg cell from the mother Jan 2, 2018 · The history of stem cell therapies is one of a limited number of clinical applications despite a vast therapeutic potential. Skin is an example: skin wounds are repaired by skin stem cells, similarly, liver damage is repaired by liver stem cells. Skin stem cells can replenish the epidermis and make hair follicle cells. The use of human embryonic stem cells (hESCs) is particularly contentious, as it involves Mar 28, 2018 · 4 min read. Tremendous controversy has surrounded efforts to undertake research on totipotent human stem cells. These criteria are designed to be technically and financially feasible and, when implemented, enhance the reproducibility and rigor of stem cell research. In theory, the treatment of human disease could be revolutionized by the ability to generate any cell, tissue, or even organ, ‘on demand’ in the laboratory. Aug 6, 2022 · Stem cell therapy is a novel therapeutic approach that utilizes the unique properties of stem cells, including self-renewal and differentiation, to regenerate damaged cells and tissues in the Apr 25, 2008 · Researchers have also combined mouse embryonic stem cells and trophoblast stem cells to create “synthetic embryos,” which have a structure akin to pre-implantation embryos (Rivron et al. Thus, molecular biologists, pharmacologists, chemists, biochemists, bioinformaticians, clinical researchers put much effort Feb 11, 2004 · Embryonic stem cells have huge potential in the field of tissue engineering and regenerative medicine as they hold the capacity to produce every type of cell and tissue in the body. When stem cells divide, they can form more stem cells or other cells that perform specialized functions. Anthony King. Stem cells are important due to their various properties such as self-renewal and differentiating into specialized cells. The potential that stem cells Stem cell research offers unprecedented opportunities for developing new medical therapies for debilitating diseases and a new way to explore fundamental questions of biology. e. Where do stem cells come from? There are several sources of stem cells used in research. Stem Cells: A Renaissance in Human Biology Research. May 13, 2024 · Some researchers working on mice, for example, have found that injecting menstrual stem cells into the rodents’ blood can repair the damaged endometrium and improve fertility. In the last 12 months, the journal has published primary research Articles, Reviews, and Perspectives across a breadth of stem cell science—from Stem cells survive much longer than ordinary cells, increasing the chance that they might accumulate genetic mutations. They are considered building blocks of tissues and organs. xk uy na hr pt wd sr aw yz sn