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What is meant by pro-acinar cell?

What is meant by pro-acinar cell?


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What is meant by "pro-acinar cell" in the following sentence? progenitors/precursors?

A transient decline in Neurog3 expression from E11 to E12 coincides with peak segregation of MPCs into proximal, Ptf1aNkx6-1+ bipotent progenitors (BPs) and distal, Ptf1a+Nkx6-1 pro-acinar cells (PACs).

Thanks


'Pro-' is a general Latin preposition and English prefix with many meanings, but often in biology, as in this case, it means "before". A proacinar cell is not yet an acinar cell (a cell of the acinus) but will be. A related usage occurs with peptides such as proinsulin.

In Latin, "acinus" means a cluster of grapes. You can find 'acini' in many places, notably exocrine glands, but in this case the pancreas is discussed. With the help of Ms. Elbakyan, they tell quite a beautiful story, but the answer to this question is mostly in the first sentence of the abstract: the stem cells (multipotent pancreatic progenitor cells) can become pro-acinar cells (which become secretory tissue of the acini, producing the pancreatic digestive enzymes), or else are reserved as bipotent progenitors that create the ducts and the islets of Langerhans.


Excretion

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Excretion, the process by which animals rid themselves of waste products and of the nitrogenous by-products of metabolism. Through excretion organisms control osmotic pressure—the balance between inorganic ions and water—and maintain acid-base balance. The process thus promotes homeostasis, the constancy of the organism’s internal environment.

Every organism, from the smallest protist to the largest mammal, must rid itself of the potentially harmful by-products of its own vital activities. This process in living things is called elimination, which may be considered to encompass all of the various mechanisms and processes by which life forms dispose of or throw off waste products, toxic substances, and dead portions of the organism. The nature of the process and of the specialized structures developed for waste disposal vary greatly with the size and complexity of the organism.

Four terms are commonly associated with waste-disposal processes and are often used interchangeably, though not always correctly: excretion, secretion, egestion, and elimination.

Excretion is a general term referring to the separation and throwing off of waste materials or toxic substances from the cells and tissues of a plant or animal.

The separation, elaboration, and elimination of certain products arising from cellular functions in multicellular organisms is called secretion. Though these substances may be a waste product of the cell producing them, they are frequently useful to other cells of the organism. Examples of secretions are the digestive enzymes produced by intestinal and pancreatic tissue cells of vertebrate animals, the hormones synthesized by specialized glandular cells of plants and animals, and sweat secreted by glandular cells in the skins of some mammals. Secretion implies that the chemical compounds being secreted were synthesized by specialized cells and that they are of functional value to the organism. The disposal of common waste products should not, therefore, be considered to be of a secretory nature.

Egestion is the act of excreting unusable or undigested material from a cell, as in the case of single-celled organisms, or from the digestive tract of multicellular animals.

As defined above, elimination broadly defines the mechanisms of waste disposal by living systems at all levels of complexity. The term may be used interchangeably with excretion.


What is meant by pro-acinar cell? - Biology

Unlike NK cells of the innate immune system, B cells (B lymphocytes) are a type of white blood cell that gives rise to antibodies, whereas T cells (T lymphocytes) are a type of white blood cell that plays an important role in the immune response. T cells are a key component in the cell-mediated response—the specific immune response that utilizes T cells to neutralize cells that have been infected with viruses and certain bacteria. There are three types of T cells: cytotoxic, helper, and suppressor T cells. Cytotoxic T cells destroy virus-infected cells in the cell-mediated immune response, and helper T cells play a part in activating both the antibody and the cell-mediated immune responses. Suppressor T cells deactivate T cells and B cells when needed, and thus prevent the immune response from becoming too intense.

An antigen is a foreign or “non-self” macromolecule that reacts with cells of the immune system. Not all antigens will provoke a response. For instance, individuals produce innumerable “self” antigens and are constantly exposed to harmless foreign antigens, such as food proteins, pollen, or dust components. The suppression of immune responses to harmless macromolecules is highly regulated and typically prevents processes that could be damaging to the host, known as tolerance.

The innate immune system contains cells that detect potentially harmful antigens, and then inform the adaptive immune response about the presence of these antigens. An antigen-presenting cell (APC) is an immune cell that detects, engulfs, and informs the adaptive immune response about an infection. When a pathogen is detected, these APCs will phagocytose the pathogen and digest it to form many different fragments of the antigen. Antigen fragments will then be transported to the surface of the APC, where they will serve as an indicator to other immune cells. Dendritic cells are immune cells that process antigen material they are present in the skin (Langerhans cells) and the lining of the nose, lungs, stomach, and intestines. Sometimes a dendritic cell presents on the surface of other cells to induce an immune response, thus functioning as an antigen-presenting cell. Macrophages also function as APCs. Before activation and differentiation, B cells can also function as APCs.

After phagocytosis by APCs, the phagocytic vesicle fuses with an intracellular lysosome forming phagolysosome. Within the phagolysosome, the components are broken down into fragments the fragments are then loaded onto MHC class I or MHC class II molecules and are transported to the cell surface for antigen presentation, as illustrated in Figure 1. Note that T lymphocytes cannot properly respond to the antigen unless it is processed and embedded in an MHC II molecule. APCs express MHC on their surfaces, and when combined with a foreign antigen, these complexes signal a “non-self” invader. Once the fragment of antigen is embedded in the MHC II molecule, the immune cell can respond. Helper T- cells are one of the main lymphocytes that respond to antigen-presenting cells. Recall that all other nucleated cells of the body expressed MHC I molecules, which signal “healthy” or “normal.”

Figure 1. An APC, such as a macrophage, engulfs and digests a foreign bacterium. An antigen from the bacterium is presented on the cell surface in conjunction with an MHC II molecule Lymphocytes of the adaptive immune response interact with antigen-embedded MHC II molecules to mature into functional immune cells.


How are Embryonic Stem Cells Collected?

While there was once a concern that embryonic stem cells were being harvested without consent from unknowing women, the vast majority are now ethically harvested an in vitro fertilization clinics. In these clinics, in order to get a successful pregnancy, many eggs must be fertilized. Only one is implanted, and with the woman’s consent, the rest can be used to harvest embryonic stem cells. To do this, scientists extract some embryonic stem cells from an embryo when it is only a small ball of cells. This can be seen in the image below.

A harvested embryonic stem cell is placed in a petri dish with nutrients and is allowed to divide. Without any signals from the embryo, the cells remain pluripotent. They continue dividing, fill one dish, and they are transferred to many more dishes and continue to grow. After 6 months of this, they are considered a successful pluripotent embryonic stem cell line. They can then be used to study disease, be used in treatments, or be manipulated genetically to provide models for how cells work.

To test that these cells are indeed pluripotent stem cells, they are injected into mice with depressed immune systems. The mice must have depressed immune systems, or their bodies would naturally reject the human tissue. Once implanted into the mouse, successful pluripotent cells will form a small tumor called a teratoma. This small tumor has different tissue types and proves that the cell line is still pluripotent and can differentiate into different cell types.


Parts of a Plant Cell

The plant cell has many different features that allow it to carry out its functions. Each of these structures, called organelles, carry out a specialized role.

Animal and plant cells share many common organelles, which you can find out more about by visiting the “Animal Cell” article. However, there are some specialized structures in plant cells, including chloroplasts, a large vacuole, and the cell wall.

Chloroplasts

Chloroplasts are specialized organelles found only in plants and some types of algae. These organelles carry out the process of photosynthesis, which turns water, carbon dioxide, and light energy into nutrients from which the plant can obtain energy. There can be over one hundred chloroplasts in certain plant cells.

Chloroplasts are disk-shaped organelles that are surrounded by a double membrane. The outer membrane forms the external surface of the chloroplast and is relatively permeable to small molecules, allowing substances entry into the organelle. The inner membrane lies just beneath the outer membrane and is less permeable to external substances.

Between the outer and inner membrane is a thin intermembrane space that is about 10-20 nanometers wide. The center of the chloroplast that is enclosed by the double membrane is a fluid matrix called the stroma (you can think of this like the cytoplasm of the chloroplast).

Within the stroma, there are many structures called thylakoids, which look like flattened disks. Thylakoids are stacked on top of one another in vascular plants in stacks called grand. Thylakoids have a high concentration of chlorophyll and carotenoids, which are pigments that capture light energy from the sun. The molecule chlorophyll is also what gives plants their green color.

Vacuoles

Plant cells are unique in that they have a large central vacuole. A vacuole is a small sphere of plasma membrane within the cell that can contain fluid, ions, and other molecules. Vacuoles are essentially just large vesicles. They can be found in the cells of many different organisms. However, plant cells characteristically have a large vacuole that can take up anywhere from 30% to as much as 90% of the total cell volume.

The central vacuole of a plant cell helps maintain its turgor pressure, which is the pressure of the contents of the cell pushing against the cell wall. A plant thrives best when its cells have high turgidity, and this occurs when the central vacuole is full of water. If turgor pressure in the plants decreases, the plants begin to wilt. Plant cells fare best in hypotonic solutions, where there is more water in the environment than in the cell. Under these conditions, water rushes into the cell by osmosis, and turgidity is high.

Animal cells, in comparison, can lyse if too much water rushes in they fare better in isotonic solutions, where the concentration of solutes in the cell and in the environment is equal, and the net movement of water in and out of the cell is the same.

Many animal cells also have vacuoles, but these are much smaller and tend to play a less crucial function.

Cell Wall

The cell wall is a tough layer found on the outside of the plant cell that gives it strength and also maintains high turgidity. In plants, the cell wall contains mainly cellulose, along with other molecules like hemicellulose, pectin, and lignins. The composition of the plant cell wall differentiates it from the cell walls of other organisms.

For example, fungi cell walls contain chitin, and bacterial cell walls contain peptidoglycan. These substances are not found in plants. Importantly, the main difference between plant and animal cells is that plant cells have a cell wall, while animal cells do not.

Plant cells have a primary cell wall, which is a flexible layer formed on the outside of a growing plant cell. Plants can also have a secondary cell wall, a tough, thick layer formed inside the primary plant cell wall when the cell is mature.

Other Organelles

Plant cells have many other organelles that are essentially the same as organelles in other types of eukaryotic cells, such as animal cells.

  • The nucleus contains deoxyribonucleic acid (DNA), the cell’s genetic material. DNA contains instructions for making proteins, which controls all of the body’s activities. The nucleus also regulates the growth and division of the cell.
  • Proteins are synthesized in ribosomes, modified in the endoplasmic reticulum, and folded, sorted, and packaged into vesicles in the Golgi apparatus.
  • Mitochondria are also found in plant cells. They produce ATP through cellular respiration. Photosynthesis in the chloroplasts provides the nutrients that mitochondria break down for use in cellular respiration. Interestingly, both chloroplasts and mitochondria are thought to have formed from bacteria being engulfed by other cells in an endosymbiotic (mutually beneficial) relationship, and they did so independently of each other.
  • The liquid within the cells is the cytosol. It is mostly made of water, and also contains ions, proteins, and small molecules. Cytosol and all the organelles within it, except for the nucleus, are called the cytoplasm.
  • The cytoskeleton is a network of filaments and tubules found throughout the cytoplasm of the cell. It has many functions it gives the cell shape, provides strength, stabilizes tissues, anchors organelles within the cell, and has a role in cell signaling. The cell membrane, a double phospholipid layer, surrounds the entire cell.

Causes

There are multiple factors that can cause cells to become precancerous, and these vary depending upon the particular type of cells involved. In the past, researchers believed the damage was done when a cell was transformed to a precancerous state by carcinogens in the environment.

We are now learning (in a field called epigenetics) that our cells are more resilient than that and factors in our environment (whether carcinogens, hormones or perhaps even stress) work together to determine what direction abnormal changes in a cell may go.  

A simplistic way of understanding causes is to look at influences in the environment that might damage healthy cells, leading to changes in the cell’s DNA, which can subsequently lead to abnormal growth and development.

Infection

Infections with viruses, bacteria, and parasites are responsible for 15% to 20% of cancers worldwide (this figure is lower in the U.S. and other developed countries).  

Infection with the human papillomavirus (HPV) can cause inflammation, leading to precancerous cells in the cervix. HPV is also an important cause of dysplasia that precedes many head and neck cancers, such as tongue cancer and throat cancer.

Most infections with HPV clear before any abnormal cell changes take place. If dysplasia develops, it may resolve on its own or with treatment, or progress to cervical cancer without treatment.  

Infection and subsequent inflammation with the bacteria Helicobacter pylori (H. pylori) can result in chronic atrophic gastritis, an inflammatory precancerous change in the lining of the stomach that can lead to stomach cancer.  

Chronic Inflammation

Chronic inflammation in tissue can lead to precancerous changes that may in turn progress to cancer. An example is in people who have gastroesophageal reflux disease (GERD) for a prolonged period of time. Chronic inflammation of the esophagus by stomach acids can result in a condition known as Barrett’s esophagus.

Among people with Barrett’s esophagus, approximately 0.5% per year will develop esophageal cancer. An important area of research is determining whether or not removing areas of high-grade dysplasia will decrease the risk of developing esophageal cancer.  

Another example is inflammation of the colon in people with inflammatory bowel disease (IBD). IBD can lead to polyps with colon dysplasia, which in turn can eventually lead to colon cancer.  

Chronic Irritation

Chronic irritation of the airways from tobacco smoke, air pollution, and some industrial chemicals can result in bronchial dysplasia (dysplasia of the bronchi). If this is detected early—during a bronchoscopy and a biopsy, for example—the precancerous cells may sometimes be treated with cryosurgery before they have the opportunity to progress to lung cancer.


There are two types of cells: prokaryotes and eukaryotes.

Prokaryotes were the first of the two to develop and do not have a self-contained nucleus. Their mechanisms are simpler than later-evolved eukaryotes, which contain a nucleus that envelops the cell's DNA and some organelles. [3]

Prokaryotes Edit

Prokaryotes have DNA located in an area called the nucleoid, which is not separated from other parts of the cell by a membrane. There are two domains of prokaryotes: bacteria and archaea. Prokaryotes have fewer organelles than eukaryotes. Both have plasma membranes and ribosomes (structures that synthesize proteins [ clarification needed ] and float free in cytoplasm). Two unique characteristics of prokaryotes are fimbriae (finger-like projections on the surface of a cell) and flagella (threadlike structures that aid movement). [2]

Eukaryotes Edit

Eukaryotes have a nucleus where DNA is contained. They are usually larger than prokaryotes and contain many more organelles. The nucleus, the feature of a eukaryote that distinguishes it from a prokaryote, contains a nuclear envelope, nucleolus and chromatin. In cytoplasm, endoplasmic reticulum (ER) synthesizes [ clarification needed ] membranes and performs other metabolic activities. There are two types, rough ER (containing ribosomes) and smooth ER (lacking ribosomes). The Golgi apparatus consists of multiple membranous sacs, responsible for manufacturing and shipping out materials such as proteins. Lysosomes are structures that use enzymes to break down substances through phagocytosis, a process that comprises endocytosis and exocytosis. In the mitochondria, metabolic processes such as cellular respiration occur. The cytoskeleton is made of fibers that support the structure of the cell and help the cell move. [2]

There are different ways through which cells can transport substances across the cell membrane. The two main pathways are passive transport and active transport. Passive transport is more direct and does not require the use of the cell's energy. It relies on an area that maintains a high-to-low concentration gradient. Active transport uses adenosine triphosphate (ATP) to transport a substance that moves against its concentration gradient. [4] [ page needed ]

Movement of proteins Edit

The pathway for proteins to move in cells starts at the ER. Lipids and proteins are synthesized [ clarification needed ] in the ER, and carbohydrates are added to make glycoproteins. Glycoproteins undergo further synthesis [ clarification needed ] in the Golgi apparatus, becoming glycolipids. Both glycoproteins and glycolipids are transported into vesicles to the plasma membrane. The cell releases secretory proteins known as exocytosis. [2]

Transport of ions Edit

Ions travel across cell membranes through channels, pumps or transporters. In channels, they move down an electrochemical gradient to produce electrical signals. Pumps maintain electrochemical gradients. The main type of pump is the Na/K pump. It moves 3 sodium ions out of a cell and 2 potassium ions into a cell. The process converts one ATP molecule to adenosine diphosphate (ADP) and Phosphate. [ clarification needed ] In a transporter, ions use more than one gradient to produce electrical signals. [3]

Endocytosis in animal cells Edit

Endocytosis is a form of active transport where a cell takes in molecules, using the plasma membrane, and packages them into vesicles. [2] : 139–140

Phagocytosis Edit

In phagocytosis, a cell surrounds particles including food particles through an extension of the pseudopods, which are located on the plasma membrane. The pseudopods then package the particles in a food vacuole. The lysosome, which contains hydrolytic enzymes, then fuses with the food vacuole. Hydrolytic enzymes, also known as digestive enzymes, then digest the particles within the food vacuole. [2] : 139–140

Pinocytosis Edit

In pinocytosis, a cell takes in ("gulps") extracellular fluid into vesicles, which are formed when plasma membrane surrounds the fluid. The cell can take in any molecule or solute through this process. [2] : 139–140

Receptor-mediated endocytosis Edit

Receptor-mediated endocytosis is a form of pinocytosis where a cell takes in specific molecules or solutes. Proteins with receptor sites are located on the plasma membrane, binding to specific solutes. The receptor proteins that are attached to the specific solutes go inside coated pits, forming a vesicle. The vesicles then surround the receptors that are attached to the specific solutes, releasing their molecules. Receptor proteins are recycled back to the plasma membrane by the same vesicle. [2] : 139–140


Acknowledgements

The authors thank Dr. Mingfu Wu (Albany Medical College) for the adenoviral vector for the expression of Cre-Recombinase, Dr. Lydia Sorokin (University of Muenstar, Germany) for the antibody to the α5 chain of laminin, Deborah Moran for her assistance with the preparation of this manuscript and associated Figures, and Scott Lyons for technical support. This research was supported by NIH grant R01-GM-51540 to S. E. LaFlamme, and in part by NIH grant R01-CA-129637 to C.M. DiPersio


Contents

Most progenitors are described as oligopotent. In this point of view, they may be compared to adult stem cells. But progenitors are said to be in a further stage of cell differentiation. They are in the “center” between stem cells and fully differentiated cells. The kind of potency they have depends on the type of their "parent" stem cell and also on their niche. Some progenitor cells were found during research, and were isolated. After their marker was found, it was proven that these progenitor cells could move through the body and migrate towards the tissue where they are needed. [ citation needed ] Many properties are shared by adult stem cells and progenitor cells.

Progenitor cells have become a hub for research on a few different fronts. Current research on progenitor cells focuses on two different applications: regenerative medicine and cancer biology. Research on regenerative medicine has focused on progenitor cells, and stem cells, because their cellular senescence contributes largely to the process of aging. [4] Research on cancer biology focuses on the impact of progenitor cells on cancer responses, and the way that these cells tie into the immune response. [5]

The natural aging of cells, called their cellular senescence, is one of the main contributors to aging on an organismal level. [6] There are a few different ideas to the cause behind why aging happens on a cellular level. Telomere length has been shown to positively correlate to longevity. [7] [8] Increased circulation of progenitor cells in the body has also positively correlated to increased longevity and regenerative processes. [9] Endothelial progenitor cells (EPCs) are one of the main focuses of this field. They are valuable cells because they directly precede endothelial cells, but have characteristics of stem cells. These cells can produce differentiated cells to replenish the supply lost in the natural process of aging, which makes them a target for aging therapy research. [10] This field of regenerative medicine and aging research is still currently evolving.

Recent studies have shown that haematopoietic progenitor cells contribute to immune responses in the body. They have been shown to respond a range of inflammatory cytokines. They also contribute to fighting infections by providing a renewal of the depleted resources caused by the stress of an infection on the immune system. Inflammatory cytokines and other factors released during infections will activate haematopoietic progenitor cells to differentiate to replenish the lost resources. [11]

The characterization or the defining principle of progenitor cells, in order to separate them from others, is based on the different cell markers rather than their morphological appearance. [12]

    found in muscles. They play a major role in muscle cell differentiation and injury recoveries. formed in the subventricular zone. [13] Some of these transit amplifying neural progenitors migrate via rostral migratory stream to the olfactory bulb and differentiate further into specific types of neural cells. found in developing regions of the brain, most notably the cortex. These progenitor cells are easily identified by their long radial process. found in the epidermis and make up 10% of progenitor cells. They are often classed as stem cells due to their high plasticity and potential for unlimited capacity for self-renewal. contains progenitor cells that develop into osteoblasts and chondroblasts. are among the most studied progenitors. [14] They are used in research to develop a cure against diabetes type-1.
  • Angioblasts or endothelial progenitor cells (EPC). These are very important for research on fracture and wounds healing. [15] are involved in generation of B- and T-lymphocytes, which participate in immune responses. [16][14] from the neural crest form a barrier between the cells of the central nervous system and cells of the peripheral nervous system. [17]

Before embryonic day 40 (E40), progenitor cells generate other progenitor cells after that period, progenitor cells produce only dissimilar mesenchymal stem cell daughters. The cells from a single progenitor cell form a proliferative unit that creates one cortical column these columns contain a variety of neurons with different shapes. [18]


Contents

In vitro (Latin: in glass often not italicized in English usage [1] [2] [3] ) studies are conducted using components of an organism that have been isolated from their usual biological surroundings, such as microorganisms, cells, or biological molecules. For example, microorganisms or cells can be studied in artificial culture media, and proteins can be examined in solutions. Colloquially called "test-tube experiments", these studies in biology, medicine, and their subdisciplines are traditionally done in test tubes, flasks, Petri dishes, etc. They now involve the full range of techniques used in molecular biology, such as the omics.

In contrast, studies conducted in living beings (microorganisms, animals, humans, or whole plants) are called in vivo.

Examples of in vitro studies include: the isolation, growth and identification of cells derived from multicellular organisms (in cell or tissue culture) subcellular components (e.g. mitochondria or ribosomes) cellular or subcellular extracts (e.g. wheat germ or reticulocyte extracts) purified molecules (such as proteins, DNA, or RNA) and the commercial production of antibiotics and other pharmaceutical products. Viruses, which only replicate in living cells, are studied in the laboratory in cell or tissue culture, and many animal virologists refer to such work as being in vitro to distinguish it from in vivo work in whole animals.

    is a method for selective replication of specific DNA and RNA sequences in the test tube. involves the isolation of a specific protein of interest from a complex mixture of proteins, often obtained from homogenized cells or tissues. is used to allow spermatozoa to fertilize eggs in a culture dish before implanting the resulting embryo or embryos into the uterus of the prospective mother. refers to a wide range of medical and veterinary laboratory tests that are used to diagnose diseases and monitor the clinical status of patients using samples of blood, cells, or other tissues obtained from a patient.
  • In vitro testing has been used to characterize specific adsorption, distribution, metabolism, and excretion processes of drugs or general chemicals inside a living organism for example, Caco-2 cell experiments can be performed to estimate the absorption of compounds through the lining of the gastrointestinal tract [4] The partitioning of the compounds between organs can be determined to study distribution mechanisms [5] Suspension or plated cultures of primary hepatocytes or hepatocyte-like cell lines (HepG2, HepaRG) can be used to study and quantify metabolism of chemicals. [6] These ADME process parameters can then be integrated into so called "physiologically based pharmacokinetic models" or PBPK.

In vitro studies permit a species-specific, simpler, more convenient, and more detailed analysis than can't be done with the whole organism. Just as studies in whole animals more and more replace human trials, so are in vitro studies replacing studies in whole animals.

Simplicity Edit

Living organisms are extremely complex functional systems that are made up of, at a minimum, many tens of thousands of genes, protein molecules, RNA molecules, small organic compounds, inorganic ions, and complexes in an environment that is spatially organized by membranes, and in the case of multicellular organisms, organ systems. [7] These myriad components interact with each other and with their environment in a way that processes food, removes waste, moves components to the correct location, and is responsive to signalling molecules, other organisms, light, sound, heat, taste, touch, and balance.

This complexity makes it difficult to identify the interactions between individual components and to explore their basic biological functions. In vitro work simplifies the system under study, so the investigator can focus on a small number of components. [8] [9]

For example, the identity of proteins of the immune system (e.g. antibodies), and the mechanism by which they recognize and bind to foreign antigens would remain very obscure if not for the extensive use of in vitro work to isolate the proteins, identify the cells and genes that produce them, study the physical properties of their interaction with antigens, and identify how those interactions lead to cellular signals that activate other components of the immune system.

Species specificity Edit

Another advantage of in vitro methods is that human cells can be studied without "extrapolation" from an experimental animal's cellular response. [10]

Convenience, automation Edit

In vitro methods can be miniaturized and automated, yielding high-throughput screening methods for testing molecules in pharmacology or toxicology. [11]

The primary disadvantage of in vitro experimental studies is that it may be challenging to extrapolate from the results of in vitro work back to the biology of the intact organism. Investigators doing in vitro work must be careful to avoid over-interpretation of their results, which can lead to erroneous conclusions about organismal and systems biology. [12]

For example, scientists developing a new viral drug to treat an infection with a pathogenic virus (e.g. HIV-1) may find that a candidate drug functions to prevent viral replication in an in vitro setting (typically cell culture). However, before this drug is used in the clinic, it must progress through a series of in vivo trials to determine if it is safe and effective in intact organisms (typically small animals, primates, and humans in succession). Typically, most candidate drugs that are effective in vitro prove to be ineffective in vivo because of issues associated with delivery of the drug to the affected tissues, toxicity towards essential parts of the organism that were not represented in the initial in vitro studies, or other issues. [13]

Results obtained from in vitro experiments cannot usually be transposed, as is, to predict the reaction of an entire organism in vivo. Building a consistent and reliable extrapolation procedure from in vitro results to in vivo is therefore extremely important. Solutions include:

  • Increasing the complexity of in vitro systems to reproduce tissues and interactions between them (as in “human on chip” systems) [14]
  • Using mathematical modeling to numerically simulate the behavior of the complex system, where the in vitro data provide model parameter values [15]

These two approaches are not incompatible better in vitro systems provide better data to mathematical models. However, increasingly sophisticated in vitro experiments collect increasingly numerous, complex, and challenging data to integrate. Mathematical models, such as systems biology models, are much needed here. [ citation needed ]

Extrapolating in pharmacology Edit

In pharmacology, IVIVE can be used to approximate pharmacokinetics (PK) or pharmacodynamics (PD). [ citation needed ] Since the timing and intensity of effects on a given target depend on the concentration time course of candidate drug (parent molecule or metabolites) at that target site, in vivo tissue and organ sensitivities can be completely different or even inverse of those observed on cells cultured and exposed in vitro. That indicates that extrapolating effects observed in vitro needs a quantitative model of in vivo PK. Physiologically based PK (PBPK) models are generally accepted to be central to the extrapolations. [16]

In the case of early effects or those without intercellular communications, the same cellular exposure concentration is assumed to cause the same effects, both qualitatively and quantitatively, in vitro and in vivo. In these conditions, developing a simple PD model of the dose–response relationship observed in vitro, and transposing it without changes to predict in vivo effects is not enough. [17]


Watch the video: Pancreatic Acinar Cell Lab (July 2022).


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