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All company, product, and brand names are trademarks or registered trademarks of their respective holders. Regenerative medicine is a broad definition for innovative medical therapies that will enable the body to repair, replace, restore and regenerate damaged or diseased cells, tissues and organs. This broad field encompasses a variety of research areas including cell therapy, tissue engineering, biomaterials engineering, growth factors and transplantation science.
The FDA defines cell therapy as, a€?The prevention, treatment, cure or mitigation of disease or injuries in humans by the administration of autologous, allogeneic or xenogeneic cells that have been manipulated or altered ex vivo.a€?1 The goal of cell therapy, overlapping with that of regenerative medicine, is to repair, replace or restore damaged tissues or organs. Cell therapy may take the form of a stem cell transplant such as a hematopoietic cell transplant that is used to restore the blood and immune system of patients with leukemia, lymphoma or other blood disorders. Activation of the bodya€™s own immune system to fight cancer is referred to as adoptive immunotherapy. Regardless of the type of cellular therapy, production of the therapeutic product may require several complex techniques to alter or manipulate the cell.
A stem cell is a cell (either adult or embryonic) that is capable of indefinite renewal through cell division and retention of its generic or unspecialized state while at the same time maintaining its potential to give rise to daughter cells of a more specialized type. Classification of stem cells as totipotent, pluripotent and multipotent describes the breadth of the stem cellsa€™ ability to create specialized cell types. Totipotent stem cells are known as the a€?mastera€? cells of the body because they have the capacity to differentiate into the 216 specialized cell types that comprise the human body plus the placenta. Pluripotent stem cells are highly versatile cells and can give rise to any specialized cell type in the body except those needed to develop a fetus.
Multipotent stem cells can give rise to several specialized daughter cells but are limited to the particular tissue, organ or physiological system of origin. Scientists expect enormous benefits from stem cell research and anticipate that it will revolutionize the practice of medicine. Embryonic stem cells are derived from embryos, specifically the inner cell mass of a blastocyst, a hollow ball of cells that forms approximately five days after conception.
Embryonic stem cells are pluripotent, meaning they have the ability to differentiate into any of the 200-plus cell types required by the body. Most embryonic stem cells used for research today have been donated from excess blastocysts created during in-vitro fertilization. Adult (Somatic) stem cells are unspecialized cells that are found in different parts of the body and, depending on the source tissue, have different properties. Adult stem cells are multipotent, meaning that they appear to be limited in the cell types that they can produce based on current evidence.
Hematopoietic stem cells that give rise to all blood and immune cells are today the most understood of the adult stem cells. Cord blood, which traditionally has been discarded, has emerged as an alternative source of hematopoietic stem cells for the treatment of leukemia, lymphoma and other lethal blood disorders.
Regardless of the adult stem cells' source a€“ bone marrow, umbilical cord blood or other tissues a€“ these cells are present in minute quantities. Multipotent stem cells for transplant from bone marrow were used experimentally from the 1950a€™s and 1960's with the work of Thomas and Storb and others, leading to stem cell transplant in the 1970's for hematologic malignancies.
Adult stem cells have been found in the bone marrow, peripheral blood and umbilical cord blood. Bone marrow transplants have been used for the past 40 years to regenerate the blood and immune systems of patients with leukemia, lymphoma, severe aplastic anemia or inherited metabolic diseases. Stem cells from Umbilical Cord Blood (UCB) have emerged as an alternative to bone marrow transplants, providing an easily obtainable and readily available source of treatment. In addition to regenerating the blood and immune systems, scientists anticipate that stem cells will be used to replace damaged or diseased tissues and organs.
As basic research continues, researchers hope to learn how cells replicate and give rise to specialized daughter cells, which may provide insight into inborn cell errors that cause birth defects. Cancer vaccines, a type of adoptive immunotherapy, are in clinical trials for prostrate, breast, ovarian and colorectal cancers. Before cell therapies move from basic research laboratories and into widespread use in the clinic, several technical obstacles must be overcome. Understand and control the mechanism of turning undifferentiated cells into specialized cells. Control the differentiation of stem cells to target cell types needed to treat disease such that sufficient quantities of the correct stem cell or differentiated cell can be generated for treatment. Learn to make stem cell transplants patient-compatible to avoid rejection by the immune system.
Demonstrate clinical improvement and normal cell development and function once stem cells have been transplanted into the patienta€™s body. Application of Current Statutory Authorities to Human Somatic Cell Therapy Products and Gene Therapy Products, Notice, Oct 14, 1993 (Federal Register).
Civil law and criminal law are two broad and separate entities of law with separate sets of laws and punishments.
Civil LawCriminal LawDefinition Civil law deals with the disputes between individuals, organizations, or between the two, in which compensation is awarded to the victim. Criminal law is the body of law that deals with crime and the legal punishment of criminal offenses.
Purpose To deal with the disputes between individuals, organizations, or between the two, in which compensation is awarded to the victim. To maintain the stability of the state and society by punishing offenders and deterring them and others from offending. Decision Defendant can be found liable or not liable, the judge decides this.
Burden of proof Claimant must give proof however, the burden may shift to the defendant in situations of Res Ipsa Loquitur (The thing speaks for itself).
Type of punishment Compensation (usually financial) for injuries or damages, or an injunction in nuisance. A guilty defendant is subject to Custodial (imprisonment) or Non-custodial punishment (fines or community service). Appeals Either party (claimant or defendant) can appeal a court's decision.
Jury opinion In cases of civil law, the opinion of the jury may not have to be unanimous. In the criminal justice system, the jury must agree unanimously before a defendant is convicted.
In civil law, a case commences when a complaint is filed by a party, which may be an individual, an organization, a company or a corporation, against another party. In case of criminal law, the burden of proof lies with the government in order to prove that the defendant is guilty.
In criminal case once a person has been convicted the complainant has no powers whatsoever to forgive. I need to identify in my assignment the stages of law used in the UK, I have statutory law, Common Law, European law and the supreme courts? Before any immune factors are triggered, the skin functions as a continuous, impassable barrier to potentially infectious pathogens. Despite these barriers, pathogens may enter the body through skin abrasions or punctures, or by collecting on mucosal surfaces in large numbers that overcome the mucus or cilia. The binding of PRRs with PAMPs triggers the release of cytokines, which signal that a pathogen is present and needs to be destroyed along with any infected cells. One subclass of cytokines is the interleukin (IL), so named because they mediate interactions between leukocytes (white blood cells).
A second class of early-acting cytokines is interferons, which are released by infected cells as a warning to nearby uninfected cells. In response to interferons, uninfected cells alter their gene expression, which increases the cells’ resistance to infection. The first cytokines to be produced are pro-inflammatory; that is, they encourage inflammation, the localized redness, swelling, heat, and pain that result from the movement of leukocytes and fluid through increasingly permeable capillaries to a site of infection. Neutrophils and eosinophils are particularly important leukocytes that engulf large pathogens, such as bacteria and fungi. Cytokines also send feedback to cells of the nervous system to bring about the overall symptoms of feeling sick, which include lethargy, muscle pain, and nausea. Watch this 23-second stop-motion video showing a neutrophil that searches for and engulfs fungus spores during an elapsed time of about 79 minutes.
Lymphocytes are leukocytes that are histologically identifiable by their large, darkly staining nuclei; they are small cells with very little cytoplasm, as shown in [link].
An infected cell (or a tumor cell) is usually incapable of synthesizing and displaying MHC I molecules appropriately.
NK cells are always active; an interaction with normal, intact MHC I molecules on a healthy cell disables the killing sequence, and the NK cell moves on. An array of approximately 20 types of soluble proteins, called a complement system, functions to destroy extracellular pathogens. The innate immune system serves as a first responder to pathogenic threats that bypass natural physical and chemical barriers of the body. Although interferons have several effects, they are particularly useful against infections with which type of pathogen? Which innate immune system component uses MHC I molecules directly in its defense strategy? Different MHC I molecules between donor and recipient cells can lead to rejection of a transplanted organ or tissue. If the MHC I molecules expressed on donor cells differ from the MHC I molecules expressed on recipient cells, NK cells may identify the donor cells as “non-self” and produce perforin and granzymes to induce the donor cells to undergo apoptosis, which would destroy the transplanted organ. If a series of genetic mutations prevented some, but not all, of the complement proteins from binding antibodies or pathogens, would the entire complement system be compromised?


The entire complement system would probably be affected even when only a few members were mutated such that they could no longer bind. HSCs were defined as single cells with lifelong ability to self-renew as well as differentiate to produce all blood cell lineages (multipotency).
The second part of review described clinical uses of HSCs isolation for cancer patients, tolerance induction and autoimmune diseases treatment. The treatment of a host of nonmalignant diseases by haplo-identical and HLA-mismatched HSCs awaits the advent of new conditioning regimens wherein the host is not in danger from the conditioning, yet pure HSCs, incapable of any GVHD, can engraft sufficiently to reverse the genetic or acquired blood cell disease.
Finally, we envision that infectious diseases of the blood system, such as AIDS, tuberculosis, malaria, and leprosy, might be treated with autologous gene-modified HSCs to produce T cells, red blood cells, and macrophages that resist colonization by the infectious agent. A very strange phenomenon concerning nomenclature has evolved in clinical hematopoietic cell transplantation. Reviews: Space-time considerations for hematopoietic stem cell transplantation by Deepta Bhattacharya.
Scientists worldwide are engaged in research activities that may enable repair of damaged heart muscle after a heart attack, replacement of skin for burn victims, restoration of movement after spinal cord injury and regeneration of pancreatic tissue to produce insulin for people with diabetes. Stem cells represent a continuum or spectrum from embryonic stem cells to adult stem cells.
For example, hematopoietic stem cells can produce many types of blood cells in the circulatory system but cannot differentiate into a brain cell. Stem cells may even lead to the creation of healthy tissues and organs for replacement of damaged and diseased body parts. Embryonic stems cells are the most primitive stem cells and as a result contain the most long-term promise for novel cell therapies and tissue regeneration.
Understanding and controlling embryonic stem cell differentiation and growth will require years of intensive research. The University of Wisconsin-Madison presents fascinating images on their Stem Cell Research web site. Adult stem cells are capable of self-renewal and give rise to daughter cells that are specialized to form the cell types found in the original body part. However, recent scientific studies suggest that adult stem cells may have more plasticity than originally thought. Hematopoietic stem cells from bone marrow have been providing lifesaving cures for leukemia and other blood disorders for over 40 years. Mesenchymal stem cells are a mixed population of cells that can form fat cells, bone, cartilage and ligaments, muscle cells, skin cells and nerve cells. Research has found that these stem cells are less mature than other adult stem cells, meaning that they are able to proliferate longer in culture and may contribute to a broader range of tissues. It has also been used as a life-saving treatment for children with infantile Krabbea€™s disease, a lysosomal storage disease that produces progressive neurological deterioration and death in early childhood.
This work coined the term a€?stem cell.a€? The first human pluripotent cells were isolated in 1998 by Dr. More recently, scientists have found stem cells in fat, skeletal muscle, skin, blood vessels, retina, liver, pancreas and the brain.
Unfortunately, the major limitation with allogenic bone marrow transplants is the availability of matched donors. UCB transplants may result in a lower incidence of transplant complications, specifically graft-versus-host disease, common in patients receiving a transplant from an unrelated donor.
Clinical trials are ongoing to repair scarred or dying heart muscle after a heart attack or during congestive heart failure. Understanding cell signaling pathways can also provide clues to how stem cells are able to hone in on the site of injury to initiate repair of damaged or diseased tissues. Stem cells may be able to bring chemotherapeutic agents directly to the targeted cancerous cells. Combining tumor cells from the patient with dendritic cells can lead to a vaccine that will seek out and destroy the cancerous cells. This involves identifying the complex signals needed to turn the genes on and off that initiate and govern the differentiation of cells. Stem cells must become integrated with the patienta€™s own tissues and learn to function as one of the patienta€™s natural body cells. Research in Focus a€“ Stem Cell Therapy from the Medical Research Council (MRC) funded through the UK Government through the Office of Science and Technology (OST). The party complaining is called the plaintiff and the party responding is called the defendant and the process is called litigation. In case of criminal law a person found guilty is punished by incarceration in a prison, a fine, or in some occasions death penalty. On the other hand, in case of civil law the burden of proof first lies with the plaintiff and then with the defendant to refute the evidence provided by the plaintiffs. Innate immunity occurs naturally because of genetic factors or physiology; it is not induced by infection or vaccination but works to reduce the workload for the adaptive immune response.
Pathogens are killed or inactivated on the skin by desiccation (drying out) and by the skin’s acidity. Some pathogens have evolved specific mechanisms that allow them to overcome physical and chemical barriers.
All viruses infect cells and replicate within those cells (intracellularly), whereas bacteria and other parasites may replicate intracellularly or extracellularly, depending on the species. A cytokine is a chemical messenger that regulates cell differentiation (form and function), proliferation (production), and gene expression to affect immune responses. One effect of interferon-induced gene expression is a sharply reduced cellular protein synthesis. The population of leukocytes that arrives at an infection site depends on the nature of the infecting pathogen. A mast cell is a leukocyte that produces inflammatory molecules, such as histamine, in response to large pathogens. These effects may have evolved because the symptoms encourage the individual to rest and prevent them from spreading the infection to others. Infected cells are identified and destroyed by natural killer (NK) cells, lymphocytes that can kill cells infected with viruses or tumor cells (abnormal cells that uncontrollably divide and invade other tissue). After the NK cell detects an infected or tumor cell, its cytoplasm secretes granules comprised of perforin, a destructive protein that creates a pore in the target cell. Cells of the liver and macrophages synthesize complement proteins continuously; these proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The proteins serve as a marker to indicate the presence of a pathogen to phagocytic cells, such as macrophages and B cells, and enhance engulfment; this process is called opsonization. Because the complement involves the binding of activated proteins in a specific sequence, when one or more proteins in the sequence are absent, the subsequent proteins would be incapable of binding to elicit the complement’s pathogen-destructive effects. You can find a lot of historical aspects of hematopoietic stem cells (HSCs) identification and isolation. Any discovery of HSCs or populations of cells enriched for HSCs should show full multipotency as well as self-renewal. In studies of experimental hematopoietic cell transplantation (HCT) and clinical HCT, grafts contain heterogeneous populations of HSCs as well as downstream progenitors and mature blood cells. HSCs that are free of cancer can form the foundation for autologous and allogeneic grafts aimed at rescuing patients from the unwanted effect of high-dose radiation and chemotherapy. Regenerative medicine promises to extend healthy life spans and improve the quality of life by supporting and activating the bodya€™s natural healing. One type of adoptive immunotherapy treatment artificially increases the number of T killer cells (a form of white blood cell) in the patient and involves collection of patient T cells, ex vivo expansion, then reinfusion to the patient. The primary distinguishing factor is plasticity - the stem cell's capacity to differentiate into multiple specialized cell types. Basic research to understand cell differentiation and human development may lead to a greater understanding of how birth defects occur. Stem cell plasticity is the ability of a stem cell from one tissue to generate the specialized cell type(s) of another tissue.
Hematopoietic stem cells are primarily found in the bone marrow but have also been found in the peripheral blood in very low numbers. Research is ongoing to determine whether umbilical cord stem cells are pluripotent or multipotent and the extent of their plasticity. Scientists are currently trying to determine how many kinds of adult stem cells exist and where they are located in the body.
UCB transplants also have less stringent requirements for donor matching compared to bone marrow transplants, increasing the likelihood that an appropriate donor can be found for patients. On-going research in diabetes is focused on understanding how stem cells might be trained to become the type of pancreatic islet cells that secrete needed insulin. Stem cells may also be used to generate liver cells or other tissues that can be used in screening new drug candidates for safety in pharmaceutical drug development. Other adoptive immunotherapies can artificially increase the number of T killer cells (a form of white blood cell) in a cancer patient.
Juries are present almost exclusively in criminal cases; virtually never involved in civil actions. In civil litigation, the plaintiff is asking the court to order the defendant to remedy a wrong, often in the form of monetary compensation to the plaintiff.
Whereas, in case of civil law the losing party has to reimburse the plaintiff, the amount of loss which is determined by the judge and is called punitive damage. In case of civil litigation if the judge or jury believes that more than 50% of the evidence favors the plaintiffs, then plaintiffs win, which is very low as compared to 99% proof for criminal law. Both the innate and adaptive levels of the immune response involve secreted proteins, receptor-mediated signaling, and intricate cell-to-cell communication. In addition, beneficial microorganisms that coexist on the skin compete with invading pathogens, preventing infection.


When pathogens do enter the body, the innate immune system responds with inflammation, pathogen engulfment, and secretion of immune factors and proteins. At least 40 types of cytokines exist in humans that differ in terms of the cell type that produces them, the cell type that responds to them, and the changes they produce. In addition to being released from cells after PAMP recognition, cytokines are released by the infected cells which bind to nearby uninfected cells and induce those cells to release cytokines, which results in a cytokine burst.
Virally infected cells produce more viruses by synthesizing large quantities of viral proteins. Both macrophages and dendritic cells engulf pathogens and cellular debris through phagocytosis.
A basophil is a leukocyte that, like a neutrophil, releases chemicals to stimulate the inflammatory response as illustrated in [link]. Cytokines also increase the core body temperature, causing a fever, which causes the liver to withhold iron from the blood. The reduced MHC I on host cells varies from virus to virus and results from active inhibitors being produced by the viruses. The complement system is so named because it is complementary to the antibody response of the adaptive immune system. Certain complement proteins can combine to form attack complexes that open pores in microbial cell membranes. When innate mechanisms are insufficient to clear an infection, the adaptive immune response is informed and mobilized. For patients with certain hematologic or advanced-stage malignancies who undergo autologous HCT, their grafts can additionally contain contaminating cancer cells.
Immune populations with specific antitumor activity can be incorporated into the grafts to capitalize on the cellular therapeutic effects. This weakening of the appropriate designation of the transplant has consequences, as clinicians not familiar with the difference between unmanipulated marrow or MPB grafts and purified or semipurified populations will be impaired in their ability to know what hematopoietic population was given, and whether cancer cells, T cells, progenitor cells, and so on comprised the transplant. The result is an increase in the number of T cells and a stronger patient immune response to the cancer.
Scientists must monitor embryonic stem cells closely and provide constant care to ensure continued growth and prevent uncontrolled or spontaneous differentiation. For example, bone marrow stromal cells are known to give rise to bone cells, cartilage cells, fat cells and other types of connective tissue (which is expected), but they may also differentiate into cardiac muscle cells and skeletal muscle cells (this was not initially thought possible). Compared to adult stem cells from other tissues, hematopoietic stem cells are relatively easy to obtain.
These cells were isolated from excess embryos obtained from in-vitro fertilization clinics. Until recently, UCB transplants were limited to pediatric patients due to the low cell stem cell dose. Repair of debilitating spinal cord injuries is also a goal of researchers through the regeneration of neurons, myelin and nerve cells.
This involves collection of patient T cells, ex vivo expansion, then reinfusion to the patient. In contrast, in criminal law, the case is filed by the government, usually referred to as the State and represented by a prosecutor, against a defendant. A criminal litigation is more serious than civil litigation, so the criminal defendants have more rights and protections than a civil defendant. In case of criminal law, defendant is not declared guilty unless approximately more than 99% proof is against him. The innate immune system developed early in animal evolution, roughly a billion years ago, as an essential response to infection. Regions of the body that are not protected by skin (such as the eyes and mucus membranes) have alternative methods of defense, such as tears and mucus secretions that trap and rinse away pathogens, and cilia in the nasal passages and respiratory tract that push the mucus with the pathogens out of the body.
When a pathogen enters the body, cells in the blood and lymph detect the specific pathogen-associated molecular patterns (PAMPs) on the pathogen’s surface. Interferons work by signaling neighboring uninfected cells to destroy RNA and reduce protein synthesis, signaling neighboring infected cells to undergo apoptosis (programmed cell death), and activating immune cells. Basophils are also involved in allergy and hypersensitivity responses and induce specific types of inflammatory responses. Without iron, certain pathogens, such as some bacteria, are unable to replicate; this is called nutritional immunity.
T cells are lymphocytes that mature in the thymus gland, and B cells are lymphocytes that mature in the bone marrow.
This process can deplete host MHC I molecules on the cell surface, which NK cells detect as “unhealthy” or “abnormal” while searching for cellular MHC I molecules. A granzyme is a protease that digests cellular proteins and induces the target cell to undergo programmed cell death, or apoptosis. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already bound by antibodies. These structures destroy pathogens by causing their contents to leak, as illustrated in [link].
Stem cells stimulated to differentiate into specialized liver cells could be used for toxicology screening during the evaluation of drug candidates. Subsequently, scientists have isolated stem cells from a variety of adult tissues, but these are multipotent, not pluripotent.
But in 2004, researchers demonstrated that combining stem cells from two UCB units could increase the cell dose to extend this lifesaving hematopoietic treatment to adult patients.
An individual can never file criminal charges against another person: an individual may report a crime, but only the government can file criminal charges in court.
If suppose you are the victim of the crime, you report it to the police and then it is their duty to investigate the matter and find the suspect . Innate immunity has a limited number of specific targets: any pathogenic threat triggers a consistent sequence of events that can identify the type of pathogen and either clear the infection independently or mobilize a highly specialized adaptive immune response. Throughout the body are other defenses, such as the low pH of the stomach (which inhibits the growth of pathogens), blood proteins that bind and disrupt bacterial cell membranes, and the process of urination (which flushes pathogens from the urinary tract). PAMPs are carbohydrate, polypeptide, and nucleic acid “signatures” that are expressed by viruses, bacteria, and parasites but which differ from molecules on host cells.
Eosinophils and basophils produce additional inflammatory mediators to recruit more leukocytes.
NK cells identify intracellular infections, especially from viruses, by the altered expression of major histocompatibility class (MHC) I molecules on the surface of infected cells. Although the clinical benefits of cell-based therapies are already being seen, unlocking the full potential of stem cells will take decades of dedicated research. Crimes are activities punishable by the government and are divided into two broad classes of seriousness: felonies having a possible sentence of more than one year incarceration and misdemeanors having a possible sentence of one year or less incarceration. In most cases, if a charge has been properly presented and if there is evidence supporting it, the Government, not the person who complains of the incident, prosecutes it in the courts. The immune system has specific cells, described in [link] and shown in [link], with receptors that recognize these PAMPs. Neutrophils have a nucleus with two to five lobes, and they contain organelles, called lysosomes, that digest engulfed pathogens. A hypersensitive immune response to harmless antigens, such as in pollen, often involves the release of histamine by basophils and mast cells. MHC I molecules are proteins on the surfaces of all nucleated cells, thus they are scarce on red blood cells and platelets which are non-nucleated.
NK cells are constantly patrolling the body and are an effective mechanism for controlling potential infections and preventing cancer progression.
After the first few complement proteins bind, a cascade of sequential binding events follows in which the pathogen rapidly becomes coated in complement proteins.
With each day, we move closer to realizing the promises of cell therapy and regenerative medicine. An eosinophil is a leukocyte that works with other eosinophils to surround a parasite; it is involved in the allergic response and in protection against helminthes (parasitic worms). The function of MHC I molecules is to display fragments of proteins from the infectious agents within the cell to T-cells; healthy cells will be ignored, while “non-self” or foreign proteins will be attacked by the immune system. On the other hand, civil law is about private disputes between individuals or between an individual and an organization or between organizations.
MHC II molecules are found mainly on cells containing antigens (“non-self proteins”) and on lymphocytes. PRRs are molecules on macrophages and dendritic cells which are in contact with the external environment. MHC II molecules interact with helper T-cells to trigger the appropriate immune response, which may include the inflammatory response.
A defendant in a civil case is found liable or not liable for damages, while in a criminal case defendant may be found guilty or not. A monocyte is a type of white blood cell that circulates in the blood and lymph and differentiates into macrophages after it moves into infected tissue. Dendritic cells bind molecular signatures of pathogens and promote pathogen engulfment and destruction. Toll-like receptors (TLRs) are a type of PRR that recognizes molecules that are shared by pathogens but distinguishable from host molecules). TLRs are present in invertebrates as well as vertebrates, and appear to be one of the most ancient components of the immune system.




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