Posted in Archive | Tagged AI / data analytics / healthtech / informatics, Analysis, Animal models, Assay development optimisation & technology, Biochemistry, Biologics / Biotechnology, Cell / tissue culture, Cell culture, Cell therapy, Cellular & Molecular biology, Cellular assays, Clinical specialities, Clinical trials, Drug development, Drug discovery, Drug targets, Flow Cytometry, Gene therapy, Genetics / genomes, High throughput screening, Imaging, Immunology, Molecular medicine, Oncology, Regenerative Medicine, Regulatory, Stem cells, System biology, Systems biology
The pharmaceutical manipulation of multipotential cells such as stem cells is therefore now primed to evolve in its own right. This article focuses on known effects of introduced biologics and small molecules, and on the future of strategies enhancing the ex vivo or in vivo regenerative properties of these remarkable cells.
Therapies targeting multipotential cells offer hope to treat many degenerative diseases caused by the premature death or malfunction of specific cell types. With a lack of suitable pharmaceutical treatments and long waiting lists for transplantable organs, such cell oriented approaches are being advanced based on either the introduction of cells into patients (ex vivo cell therapies) or the use of agents to affect cells already within the patient (in vivo therapies).
Applications For Induced Pluripotent Stem Cells In Disease Modelling And Drug Development For Heart Diseases
Cell pharmaceutics are thus the application of biological or chemical molecules to enhance these therapeutic approaches and it is an emerging area of biotechnology taking advantage of research advances in fields such as cell signalling and the use of growth factors to repair damage caused by disease, trauma and processes such as ageing.
Therapies targeting multipotential cells address numerous large healthcare markets by promising novel therapies to treat debilitating diseases such as diabetes, Parkinson’s, Huntington’s, heart disease and stroke, as well as accidental damage such as spinal cord injury. They are emerging as a potentially revolutionary way to treat malignancies, blood disorders, as well as certain inborn errors of metabolism and immunodeficiencies.
Replacement of the blood and immune systems with blood stem cells, the use of neural stem cells to treat neurodegenerative systems, the use of mesenchymal stem cells to repair bones and joints and liver stem cells for liver failure are just a few examples of clinical applications of endogenous multipotential cell targeted therapies (Figure 1).
Stem Cells Market Size, Share And Trends Report, 2030
Taking into consideration the potential therapeutic benefits and thus market opportunities, drugs designed to enhance stem cell activity have a bright future. Like the development of most pharmaceuticals, the most effective ways to discover these agents will, however, need to encompass several disparate phenomena that will be briefly reviewed in this article: the natural distribution of such multipotential cells, molecules already known to affect them, technical opportunities to expand our knowledge of such cells and pharmaceuticals, and the regulatory environment which will greet such pharmaceutical products.
Human cells that have the potential to give rise to many differentiated cell types, such as stem cells, can be found in the inner cell mass of the early embryo, in some tissues of the foetus, the umbilical cord and placenta, and in several adult organs. Sources of adult stem cells that have the potential to become specialised cell types include bone marrow, blood, the eye, brain, skeletal muscle, dental pulp, liver, skin, the lining of the gastrointestinal tract and pancreas.
Certain stem cells are rather rare, or at the least inaccessible, and thus difficult to identify and purify. When grown in culture, stem cells are difficult to maintain in an undifferentiated state and may be subject to undetected changes occurring over time. Though there is now a widespread consensus that many adult mammalian organs do contain stem cells, there is no consensus about how many populations of stem cells exist. (For that matter, the total number of cell types in the body as previously estimated based on such criteria as morphology is in flux due to more detailed data available from techniques such as molecular profiling.)
Stem Cells Bioprocessing: An Important Milestone To Move Regenerative Medicine Research Into The Clinical Arena
One reasonably well known estimate (1) is that there is one hematopoietic stem cell present in every 10, 000 to 15, 000 nucleated bone marrow cells. However, a lack of consensus on stem cell numbers can be readily seen from publications pointing out that there are no markers currently available to identify in vivo several stem cell types, and that the only method for testing whether a given population of cells contains stem cells is to isolate the cells and manipulate them in vitro (2).
These methods suffer from both qualitative inadequacies, since the process may itself change the intrinsic properties of the cells and may entirely miss many types of multipotential cells, and quantitative shortcomings, in that it remains to be seen how reflective numbers estimated from such methods will compare to numbers enumerated from actual adult tissues.
For example, the stem cells of the pancreas, which can give rise to islet cells, are usually thought to be in the pancreatic ducts, but methods of isolating them so that they can be expanded in the laboratory have not been found. Similarly, stem cells do exist in the brain and spinal cord, but are rare and tend to be in regions that are difficult to access. If insufficient numbers of stem cells turn out to limit some potential therapeutic applications it may become important to find ways to increase the numbers of multipotential cells prior to other therapeutic interventions.
Revolutionising Medicine: The Power Of Induced Pluripotent Stem Cells (ipscs)
Transdifferentiation or reprogramming may be one means to augment multipotential cell numbers. Several cell types, even including cells that appear to have terminally differentiated, may turn out to actually have the ability to ‘transdifferentiate’ into cells of completely different types under appropriate stimuli. For example, blood cells could be converted into neuronal cell types of use in treating Parkinson’s disease (Figure 2).
Once we identify the molecules that act on stem cells, we might be able to use similar molecules to recruit more stem cells to an area of damage in the body. Based upon the type and chemical composition, molecules acting on stem cells can be classified as:
Proteins which are known to act on stem cells and are used clinically include G-CSF (granulocyte colony stimulating factor (3, 4); GM-CSF (granulocyte- macrophage colony stimulating factor5; and Albugranin™ (Albumin Granulocyte Colony Stimulating Factor).
Pdf) Stem Cells Applications In Regenerative Medicine And Disease Therapeutics
AMD 3100 is an example of a drug having specific actions and effects on stem cells. Many drugs, including clozapine, cerebral vasodilators like vinpocetine, neuroleptics, anti-thyroid medications, analgesics, phenothiazine derivatives and antiinflammatory drugs are known to induce agranulocytosis and bone marrow suppression at the committed stem cell level.
Table 1 summarises the positive effects, adverse effects and primary indications for some prominent protein and drug molecules acting on stem cells.
Many aspects of cell behaviour, such as growth, motility, differentiation and apoptosis, are regulated by signals cells receive from their environment. Such signals are important during embryonal development, wound healing, hematopoiesis and in the regulation of the immune response. These signals come from the binding of soluble signalling molecules like G-CSF and GM-CSF to specific receptors at the cell membrane (6).
Potential Applications Of Different Stem Cells
Many growth factors bind to receptors which contain an intrinsic tyrosine kinase domain (7), whereas many cytokines bind to receptors devoid of kinase domains but which bind to intracellular kinases of the Jak family (8). In these cases, ligand binding induces receptor dimerisation or oligomerisation resulting in tyrosine phosphorylation of the receptors and activation of specific signalling pathways leading to cell growth, migration or the prevention of apoptosis (9).
There is a network of cytokine interactions and a cytokine cascade that allows considerable flexibility and ready amplification of response to a particular molecular stimulus. Extensive profiling of the signalling pathways underlying the redirection of cell fate is clearly needed to drive the next generation of ‘stem cell drugs’.
As high-throughput screens to identify molecules acting on multipotential cells yield more leads, and as we begin to understand more aspects of cell specificity, it will become important to be able to monitor the effect of such agents on cells within relevant animal models as well as ultimately within human subjects. Monitoring cells as they are driven towards different cell fates will also involve the development of new techniques useful for both research and pharmaceutical development purposes.
Stem Cells In The Treatment Of Disease
The two methods most commonly used to measure changes in at least hematopoietic stem cell numbers, the colony-forming unit (CFU) assay and the CD34+ assay (10), are effectively single measurement assays. The CFU assay involves growing a small portion of the stem cell collection in a culture. A single stem cell in the sample can form groups of mature blood cells, which are then microscopically counted. While the CFU assay is the best indicator of the ability of the stem cells to grow in a patient after transplantation, its major drawback is the need to wait two weeks before results can be obtained.
This limits its usefulness in determining adequacy of stem cell collection for transplants. The CD34+ assay, measuring stem cell content by counting cells displaying CD34 surface protein with a flow cytometer, can give a readout in two hours. This can help prevent a patient from needlessly undergoing a second stem cell collection when the first collection was adequate.
Tracking the in vivo biodistribution and movement of either transplanted cells or endogenous cells of interest requires techniques that
0 comments:
Post a Comment