Wednesday, October 9, 2019

Stem Cells part 31




Stem cells have a bright future  for the therapeutic world by promising stem cell therapy. We hope to see new horizon of therapeutics in the form of bone marrow transplant, skin replacement, organ development, and replacement of  lost tissue such as hairs, tooth, retina and cochlear cells.

Stem Cells part 30




Scientists and stem cell research

Scientists believe that stem cell research could lead to cures for a myriad of diseases afflicting humans. Anti-abortion groups, some religious groups, and conservative citizens say that using cells from embryos is immoral because it destroys life. However, recent news has shown that support stem cell research by a 2-1 margin and say that it should be funded by the federal government, despite controversy over the human embryos.

Stem Cells part 29




Diabetes affects millions of people in the world and is caused by the abnormal metabolism of insulin. Normally, insulin is produced and secreted by the cellular structures called the islets of langerhans in the pancreas. Recently, insulin expressing cells from mouse stem cells have been generated. In addition, the cells self assemble to form structures, which closely resemble normal pancreatic islets and produce insulin. Future research will need to investigate how to optimize conditions for insulin production with the aim of providing a stem cell-based therapy to treat diabetes to replace the constant need for insulin injections.

Stem Cells part 28




Brain cell transplantation

Stem cells can provide dopamine - a chemical lacking in victims of Parkinson's disease. It involves the loss of cells which produce the neurotransmitter dopamine. The first double-blind study of fetal cell transplant for Parkinson's disease reported survival and release of dopamine from the transplanted cells and a functional symptoms. However, some patients developed side effects, which suggested that there was an over sensitization to or too much dopamine. Although the unwanted side effects were not anticipated, the success of the experiment at the cellular level is significant.

Stem Cells part 27




Skin replacement

The knowledge of stem cells has made it possible for scientists to grow skin from a patient's plucked hair. Skin (kerayinocyte) stem cells reside in the hair  follicle and can be removed when a hair is plucked. These cells can be cultured to form an epidermal equivalent of the patients own skin and provides tissue for an autologous graft, bypassing the problem of rejection.

Stem Cells part 26




Bone marrow transplant are a well known clinical application of stem cell transplantation. Bone marrow transplant can repopulate the marrow and restore all the different cell types of blood after high doses of chemotherapy and/or radiotherapy, our main defense and used to eliminate endogenous cancer cells. The isolation of additional stem cell and progenitors cells is now being developed for many other clinical applications.

Stem Cells part 25




Possible treatments by stem cells

A number of stem cell therapeutics exist, but most are at experimental stages and/or costly, with the  notable exception of bone marrow transplantation. Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, type I diabetes mellitus, Parkinson's disease, Huntington's disease, celiac disease, cardiac failure, muscle damage and neurological disorders, and many others. They have suggested that before stem cell tharapeutics can be applied in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation as well as the mechanisms of stem cells interaction with the disease/injured microenvirontment.

Stem Cells part 24





Applications of stem cells

The goal of any stem cell therapy is to repair a damaged tissue that can't heal itself. Ongoing research on stem cell therapies gives hope to patients who would normally not receive treatment to cure their disease but just to alleviate the symptoms of their chronic illness. Stem cell therapies involve more than simply transplanting cells into the body and directing them to grow new, healthy tissue. It may also possible to coax stem cells already in the body to work overtime and produce new tissue.

Stem Cells part 23




Stem cells lines

A stem cell line is a family of constantly dividing cells, the product of a single parent group of stem cell. They are obtained from human or animal tissues and can replicate for long periods of time in vitro ("within glass", or, commonly, "in the lab"), in an artificial environment). They are frequently used for research relating to embryonic stem cells or cloning entire organism. Once stem cells have been allowed to divide and propogate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line.

Stem Cells part 22




Stem cell culture

Growing cells in the laboratory is known as cell culture. Human embryonic stem cells are generated by transferring cells from a preimplantation stage embryo into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. However, if the plated cells survive, divide and multiply enough to crowd the dish, they are removed gently and plated into several fresh culture dishes. The process of replating or sub culturing the cells is repeated many times and for many months. Each cycle of subculturing the cells is referred to as a passage. Once the cell line is established, the original cells yield millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for six or more months without differentiating, are pluripotent, and appear genetically normal are referred to as an embryonic stem cell line. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.

Stem Cells part 21




Pluripotent stem cells

Recently, a third type of stem cell, with properties similar to embryonic stem cells, has emerged. Scientists have engineered these induced pluripotent stem cells by manipulating the expression of certain genes - "reprogramming" somatic cells back to a pluripotent state.

Stem Cells part 20




Adult stem cells

Adult stem cells are undifferentiated totipotent or multipotent cells, found throughout the body after embryonic development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Unlike embryonic stem cells, which are defined by their origin (the inner cell mass of the blastocyst), the origin of adult stem cells in some mature tissues is still under investigation.

Stem Cells part 19




Embryonic stem cells

Embryonic stem cells are self-replicating pluripotent cells that are potentially immortal. They are derived from embryos at a developmental stage before the time of implantation would normally occur in the uterus. The embryos from which human embryonic stem cells are derived are typically four or five days old and are a hollow microscopic ball of cells called the blastocyst.

Stem Cells part 18




Classification of stem cells on the basis of their sources

The easiest way to categorize stem cells is by dividing them into two types:

Early or embryonic and mature or adult. Early stem cells, often called embryonic stem cells, are found in the inner cell mass of a blastocyst after approximately five days of development. Mature stem cells are found in specific mature body tissues as well as the umbilical cord and placenta after birth.

Stem Cells part 17




Unipotent

The ability to only produce cells of their own type, but have the property of self-renewal required to be labeled a stem cell. Examples include (adult) muscle stem cells.

Stem Cells part 16




Oligopotent

The ability to differentiate into a few cells. Examples include (adult) lymphoid or myeloid stem cells.

Stem Cells part 15




Multipotent

The ability to differentiate into a closely related family of cells. Examples include hematopoietic (adult) stem cells that can become red and white blood cells or platelets.

Stem Cells part 14




Pluripotent

The ability to differentiate into almost all cell types. Examples include embryonic stem cells and cells that are derived from the mesoderm, endoderm, and ectoderm germ layers that are formed in the beginning stages of embryonic stem cell differentiation.

Stem Cells part 13




Totipotent

The ability to differentiate into all possible cell types. Examples are the zygote formed at egg fertilization and the first few cells that result from the division of the zygote.

Stem Cells part 12




Classification of stem cells on the basis of potency

Stem cells can be classified by the extent to which they can differentiate into different cell types. These four main classification are totipotent, pluripotent, multipotent, or unipotent

Stem Cells part 11




Laboratory studies of stem cells enable scientists to learn about the cells essential properties and what makes them different from specialized cell types.  Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems  to study normal growth and identify the causes of birth defects. Research on stem cells continues to advance knowledge about how an organism develop from a single cell and how healthy  cells replace damaged cells in adult organisms. Stem cell research is one of the most  fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates  new discoveries. Over the past year, adult stem cells have been used either exclusively or in combination with other treatments to achieve significant "healthcare benefits" for sufferers of the every tissue of human body.

Stem Cells part 10




A stem cell is a non-specialized, generic cell which can make exact copies of itself indefinetely and can differentiate and produce specialized cells for the various tissues of the body. Stem cells are cells found in most, if not all, multi-cellular organisms. They are characterized by self renewal and potency i.e. - the ability to renew themselves through mitotic cell division and differentiating  into a diverse range of specialized cell types. They are vital to the development, growth, maintenance and repair of our brains, bones, muscles, nerves, blood, skin and other organ.

Stem Cells part 9




Over the last few years, national policies and debate among the public as well as religious groups, government officials and scientists have led to various laws and procedures regarding stem cell harvesting, development and treatment for research or diseases purposes.  The goals of such policies are to safeguard the public from unethical stem cell research and use while still supporting new advancements in the field.

Stem Cells part 8




The first published study of successful cartilage regeneration in the human knee using autologous  adult mesenchymal stem cells is published by clinicians from Regenerative Sciences in 2008. Embryonic stem cell isolated from a single human hair was was reported in 2008. Australian scientists (2009) found a way to improve chemotherapy of mouse muscle stem cells, Kim et al, 2009. Announced that they had devised a way to manipulate  skin cells to create patient specific "induced pluripotent stem cells", claiming it to be the "ultimate stem cell solution". For the first time, human embryonic stem cells have been cultured under chemically controlled conditions without the use of animal substances, which is essential for future clinical uses in 2010.

Stem Cells part 7




Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells in October 2006. It is suggested that these stem cells have the ability to differentiate into more cell types than adult stem cells, opening up greater possibilities for cell-based therapies. Then, in early 2007, researchers led by Dr. Anthony Atala claimed that a new type of stem cells had been isolated in amniotic fluid. This finding is particularly important because these stem cells could prove to be a viable alternative to the controversial use of embryonic stem cells. Mario Capecchi, Martin Evans, and Oliver Smithies won the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.

Stem Cells part 6




James Thomson and coworkers derived the first human embryonic stem cell line at the University of Wisconsin-Madison in 1998. More recently, in 2005, scientists at Kingston University in England were purported to have found another category of stem cells. These were named cord blood embryonic-like stem cells, which originate in umbilical cord blood. Korean researcher Hwang Woo-Suk (2004-2005) claimed to have created several human embryonic stem cell lines from unfertilized human oocytes.

Stem Cells part 5




The history of stem cell research had a benign, embryonic beginning in the mid 1800's with the discovery that some cells could generate other cells. In the early 1900's the first real stem cell were discovered when it was found that some cells generate blood cells. The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov in 1908. Bone marrow transplant between two siblings successfully treated SCID in1968. Haemopoietic stem cells were discovered in human cord in1978.

Stem Cells part 4




Stem cell research holds tremendous promise for the development of novel therapies for many serious diseases and injuries. While stem cell-based treatments have been established as a clinical standard of care for some conditions, such as hamatopoietic stem cell transplants for leukemia and epithelial stem sell-based treatments for burns  and corneal disorders, the scope of potential stem cell-based therapies has expanded in recent years due to advances in stem cell research. It is impossible to project when actual treatments or cures might emerge from such research, put the paths this research might take and potential applications have been much discussed. Stem cells can now be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture. Highly plastic adult  stem cells from a variety of sources, including umbilical cord blood and bone marrow, are routinely used in medical therapies.

Stem Cells part 3




For decades, researchers have been  studying the biology of stem cells to figure out how development works and to find new ways of treating health problems. The scientific researchers and medical doctors of today hope to make the legendary concept of regeneration into reality by developing therapies to restore  lost, damaged, or aging cells and tissues in the human body. This research has opened new horizons for stem cell research.

Stem Cells part 2




Stem cells are defined as cells that have clonogenic and self-renewing capabilities and differentiate into multiple cell lineages. Stem cells are found in all of us, from the early stages of human development to the end of life. Stem cells are basic cells of all multicellular organisms having the potency to differentiate into wide range  of adult cells. Self renewal and totipotency are characteristic of stem cell. Through totipotencyis shown by very early embryonic stem cells, the adult stem cells possess multipotency and differential plasticity which can be exploited for future generation of therapeutic options. All stem cells may prove useful for medical research, but each of different types has both promise and limitations.

Stem Cells part 1




Stem cells are unspecialized cells that develop into the specialized cells that make up the different types of tissue in the human body. They are characterized by the ability to renew themselves through mitotic cell division and differentiate into a diverse  range of  specialized cell types. They are vital to the development, growth, maintenance, and repair of our brains, muscles, bones, nerves, blood, skin, and other organs. Stem cell are found in all of us, from the early stages of human development to the end of life. Stem cell research holds tremendous promise for the development of novel therapies for many serious diseases and injuries. While stem cell-based treatments have been established  as a clinical standard of care for some conditions, such as hematopoietic stem cell transplants for leukemia and epithelial stem cell-based treatments for burns and corneal disorders, the scope of potential stem cell-based therapies has expanded in recent years due to advances in stem cell research. It has been only recently that scientists have understood  stem cells well enough to consider the possibilites  of growing them outside the body for long periods of time. With that advance, rigorous experiments can be conducted, and the possibility of manipulating these cells in such a way that specific tissues can be grown is real.

Wednesday, September 4, 2019

STEM CELL part 27




There is obviously a moral obligation to provide new and better treatments for patients. But there are also obstacles on the road, regulatory as well as technical. If the problem of standardization, in particular of induced pluripotent stem cell lines, is not addressed, this will create regulatory hurdles as long as the FDA regards every cell line as a new treatment. Moreover, if cell therapies are to be commercially successful and affordable, solutions to the problem of scaling up have to be found.

(Goran Hermeren, Prof. em. Medical ethics, Lund University)

STEM CELL part 26




Changes in the scientific landscape may bring about changes in the ethical landscape. Neither science nor values are static. Ongoing dialogues between different stakeholder groups on how to address the ethical issues raised by different therapies is a long term investment which will pay off, particularly if the decisions taken are regarded as preliminary and updated if and when there is new evidence or changes in the landscape of values.
(Goran Hermeren, Prof. em. Medical ethics, Lund University)

STEM CELL part 25




Finally, it is clear that all types of stem cell research, including embryonic stem cell and induced pluripotent stem cell research, must take place within a carefully considered ethical and regulatory framework, and that therapies based on living cells pose new challenges for regulators.

STEM CELL part 24




Broader ethical questions include tissue ownership, informed consent when donating cells for stem cell banking, patient safety and data protection, and access to treatments (Hug and Hermeren, 2011, Hermeren, 2012)

STEM CELL part 23




The discovery of induced pluripoten tstem cells raised the possibility that embryonic stem cells research would no longer be necessary, there be circumventing the ethical issues present in embryonic research. To date, this  has not been the case: the stem cell field continues to rely both embryonic stem cells and induced pluripotent stem cell research to progress the understanding of plurypotency and its potential applications (Smith and Blackburn, 2012). Further, it has become clear that induced pluripotent cell research is not free of ethical considerations (Hug and Hermeren, 2011). For instance, the potential of these cells to generate sperm and egg cells, or even a whole new individual, raises new ethical questions about the status of the cells themselves and how they may be used.

STEM CELL part 22




In Germany, no new human embryonic stem cell lines can be generated, but research using imported lines generated prior to May 1, 2007 is permitted, while in the USA, a series of restrictions implemented between 1995 and 2009 limited federal funding for human embryonic stem cell research. The patentability of human embryonic stem cells and lines is similarly complex (The Hinxton Group, 2013). Some countries, including the US, place liitle or no restriction on this practice, while in 2011 the European Court of Justice ruled that patents cannot be granted in Europe for any technologies based on research using human embryonic stem cells.

STEM CELL part 21




Ethics, policy and regulation

Like many areas of biomedical science, stem cell research has provoked debate regarding the ethics and regulation of the research and resulting therapies. Initiallly these discussions focused largely  on the moral status of the embryo (EuroStemCell, 2011). Goverments responded with different regulations and legislations, leading to international complexities (Kawakami et  al., 2010, Nakatsuji et al., 2007, STEMGEN, 2013). Countries including Australia, Singapore, Spain, South Korea, Belgium, the UK, and Sweden take a tightly regulated but permissive approach to research involving the use of human embryos to generate embryonic stem cell lines. Other have placed some restrictions on research in this area, either through direct legislation or by limiting the uses of research funding.

STEM CELL part 20




Finally, where use of a patient's own cells is not possible, either because a sufficient number of cells cannot be obtained or because protocols for generating the required cell type in the lab (e.g., from induced pluripotent stem cells) have not yet been developed, the consequences of immunosupprtession must also be considered. Banking human embryonic stem cell and induced pluripotent stem cell lines is one way to ensure that patients can receive cells with a good immunological match, thus minimizing any required immunosuppression (Turner et al., 2013)

STEM CELL part 19




The ability to functionally integrate transplanted cells into damaged organs is also a major challenge. For some cell types, such as pancreatic beta cells and retinal pigment epithelial cells, it appears that transplantation of the cells alone will be sufficient to ameliorate symptoms or cure the disease (in these examples, diabetes and macular degeneration, respectively). For others, it is likely that complex organ structure creation through in vitro tissue  engineering will be required. Here, the challenge is not only to derive the correct organ structure at scale, but also to maintain long-term function following transplantation. To achieve this will require new collaboration between tissue engineers and stem cell and vascular biologist, as well as improved understanding  of how stem cells are controlled by their specific environment (niche) within the body.

STEM CELL part 18




Biological challenges 

While cell replacement offers hope for the treatment of many diseases in the long term, it may still be some time before large-scele clinical use is available for most applications. Understanding how to produce many of the speialized cel types in vitro remains a major hurdle. Furthermore, the field faces challenges around quality control. It is essential that only defined cell populations are introduced into patients; this requires careful characterization of the cell populations intended for transplantation, in terms of gene expression and epigenetic profiles and functional attributes, and also to ensure that the populations do not contain other potentially harmful cell types. For cells generated from human pluripotent cells, for example, contamination of the transplant population with even a small number of residual embryonic stem cell or induced pluripotent stem cells could promote tumor formation. Additionally, as cells can acquire mutations during the culture process, stringent quality control is essential to ensure that cultured cells intended for transplantation have not acquired undesirable properties.

STEM CELL part 17




Regenerative therapies

In addition to cell replacement strategies, increased understanding of the intrinsic regenerative potential of individual organs, coupled with knowledge of how to control the scarring response in damaged tissues, may allow the development of drugs aimed at stimulating the body's own (endogenous) stem cells to initiate or enhance repair. This approach is expected to prove more suitable than cell replacement for some diseases.

STEM CELL part 16




Cell replacement therapies

Stem cell research is also anticipated to contribute to new cell-based therapies through the use of cells generated from embryonic stem cells and/or induced pluripotent stem cells, or of ex vivo tissue stem cells, to replace missing or damaged cells, and (in the future) to generate artificial organs for transplantation. Although is not yet  possible to generate many cell types in the lab, or to expand many tissue stem cell types ex vivo, clinical trials using human fetal and adult cells, as well as human embryonic stem cells and induced pluripotent stem cell-derived cells, are already in progress or on the horizon. For example, retinal pigmen epithelial cells have been produced from both human embryonic stem cells and human induced pluripotent stem cells (Carr et al., 2013, Jin et al., 2009), and both cases are conducting clinical trials to test the capacity of these pluripotent cell-derived cells to treat macular degeneration.

STEM CELL part 15




Some progress has been made towards these goals. For instance, in recent tests human embryonic stem cell-derived hepatocytes performed as well as the current FDA gold standard primary adult cells at predicting  human hepatotoxicity (Szkolnicka D et al., 2014). However, the ability to control the differentiation of both tissue and pluripotent stem cells remains a challenge for the field.

STEM CELL part 14




Induced pluripotent stem cell technology has also made it possible to conduct parallel high-throughput compound screens on defined cell types derived from a large number of different individuals. This technology will allow the screening process to account for genetic differences in the response to potential new drugs. As induced pluripotent stem cells can now be easily generated from patients, including those with inherited diseases and their unaffected relatives, they also provide a new way to investigate the molecular basis of disease-prone cells side-by-side in the lab, enabling the development of improved  pharmaceutical interventions.

STEM CELL part 13




Stem cells in drug discovery, toxicity testing, and  disease modelling

Stem cell research has the potential to improve and accelerate drug screening, drug discovery, and pre-clinical toxicological assessment of new drugs. Controlled differentiation of human pluripotent cells and/or ex vivo expansion of human tissue stem cells could produce unlimited supplies of defined human cell types. Once developed, this technology should permit screening of more compounds in shorter time and at less expense than is currently possible. Additionally, as it will allow primary screens to be conducted on human cells, it may reduce the number of promising drugs that fail in late phase II/III clinical trials because of unexpected differences between animals and humans, as well as the number of animal tests needed.

STEM CELL part 12




Three key facts about stem cells:
  • The defining characteristic of a stem cell is that it can self-renew or differentiate
  • Stem cells enable the body to grow, repair and renew
  • There are three types of stem cells (tissue stem cells, embryonic stem cells, induced pluripotent stem cells)

STEM CELL part 11




Subsequent advances, including derivation of human stem cell lines and the advent of human induced pluripotent stem cell technology, as well as progress in making specific specialized cells from stem cells in the laboratory, have suggested that stem cell therapies may be more broadly applied to aid a wide range of disorders.

STEM CELL part 10




In hematopoietic stem cell transplantation, stem cells are harvested from the patient or donor and, following leukemia treatment, are transplanted back into the patient to restore their blood and immune systems. In the case of stem cell-based skin or corneal grafting, skin or limbal stem cells are obtained from the patient, and then grown in the lab to produce sheets of cells sufficient to cover the burn or wound area. These applications exemplify two different approaches to transplanting tissue stem cells: one requires expanding cell numbers through lab culture, while the other does not.

STEM CELL part 9




Tissue stem cells have been used therapeutically for many years in the contexts of hematopoietic stem cell transplantation, a vital component in the sucessful therapy of many types of blood cancer; stem cell-based skin grafting (Green et al., 1979, Green, 1989), which can save the lives of patients with extensive third-degree burns; and limbal stem cell grafting, which can restore sight to patients with impaired vision caused by corneal damage (Rama et al., 2010).