stem cells ROSE Flashcards
what is a mesenchymal stem cell
small spindle-shaped cells with large nuclei, prominent nucleoli and fine chromatin. These are multipotent stem cells that differentiate as progenitor cells for all types of connective tissue, such as fibroblasts, osteoblasts, chondroblasts and preadipocytes
where can mesenchymal stem cells be isolated from
bone marrow, adipose tissue, cord blood, amniotic fluid, iPSC
Where may there be discrepancies in the study of the use of mesenchymal stem cells for clinical use
in in vitro vs in vivo studies there may be differences in the immune compatibility, dosing, fitness of culture adapted MSCs (how good are they at the point of delivery)
what are the 3 main modes of action of MSCs
differentiation, Paracrine effects, cell-cell effects
describe in detail how MSCs have paracrine effects
they may release signalling molecules such as cytokines, growth factors, extracellular vesicles. These effect neighboring cells. This can have an anti-inflammatory effect pro-regentive (release of growth factors) and make the immune system less aggressive
describe how MSCs have cell-cell effects
they can interact with other cells through gap junctions between cells, tunneling nanotubes and surface molecule interaction
what are the main cell types MSCs can differentiate into
osteoblasts (bone cells)
Chondrocytes (cartaliage cells)
adipocytes (fat cells)
- important for tissue repair and regeneration
what is a key application of mesenchymal stem cells
tissue repair and regeneration
what is effereocytosis
the effective clearance of apoptotic cells by professional and non professional phagocytes. cellular clean-up where immune cells “eat” dying cells before they burst and cause inflammation. This process is boosted by MSCs
why is efferocytosis important
- Prevents inflammation - Dead cells release toxic stuff if not cleaned up quickly. Efferocytosis prevents that.
- Promotes healing - After gobbling up dying cells, macrophages release anti-inflammatory and pro-healing signals.
- Controls immune responses - Helps calm the immune system after an injury or infection.
what is the reticuloendothelial system
The Reticuloendothelial System (RES) — sometimes called the mononuclear phagocyte system (MPS) — is a network of immune cells in your body that trap, engulf, and break down unwanted stuff like:
* Dead cells
* Microbes (like bacteria and viruses)
* Foreign particles (like nanoparticles or old drugs)
what is the difference between the reticuloendothelial system and efferocytosis
efferocystosis is a specific process involving only apoptotic cells whereas RES involves a network of cells such as macrophages, kupffer cells etc to clear many dead things like cells and particles, essentially anything ‘unwanted’
RES is a full defence and cleaning network whereas effereocytosis is specialised to just apoptotic cells or dying cells
how do MSCs have an anti-inflammatory effect
How MSCs effect efferocytosis
- They boost this
- They release inflammatory mediators, such as cytokines, that signal macrophages to eat dead/dying cells.
- They also reprogram macrophages (M1–>M2) to make them more efficient at efferocytosis
The removal of dead/dying cells prevents the release of toxins and upon engulfing and digesting these dead/dying cells, macrophages release anti-inflammatory signals. This helps calm the immune system following impairment by injury or infection
what is a somatic cell
any cell that is not a gamete, germ or stem cell.
what is involved in somatic cell therapy meds
contains cells or tissues that have been manipulated to change their biological characteristics - their function is now different from its usual body function. they can be used to cure, diagnose and prevent disease
what is HOLOCLAR
Limbal stem cells are extracted from a patients healthy eye and cultured and grown in the lab. They are then trasnplanted into the same patients damaged eye where there is a diseased cornea resulting in loss of vision
what is the link between holoclones, meroclones, paraclones and stratified epithelial cells
holoclones GIVE RISE TO meroclones GIVE RISE TO paraclones GIVE RISE TO stratified epithelium
as we progress, each cell type is less able to prliferate
which has the highest proliferation ability: holoclones or meroclones
holoclones
what is p63 in terms of holoclones
this is a transcription factor. High levels of its expression indicate the cell’s high ability to proliferate. Its levels are highest in holoclones and the levels decrease as cells give rise to other cells
how are holoclones that can be used in HOLOCLAR therapy identified
using p63 marker
where are holoclones mainly expressed
limbus
what is cell tourism?
Stem cell tourism is a subset of the medical tourism industry. It involves patients traveling to another country to receive stem cell therapies that may not be available, affordable, or timely in their home country. Stem cell tourism is a form of medical tourism that is advertised to the public as a proven cure. It exists chiefly because most stem cell “treatments” are unproven and not readily available from reputable local medical services.
why is stem cell torusim potentially dangerous
unproven and untested stem cells can result in injury or death
what defines an unproven cell therapy
unclear scientific rationale, lack of understanding of MOA, insurrient in vitro data, lack of SOP for safe handling and management, inadequate information disclosed to patients to obtain informed consent, non-standardised methods
what are the three main obstacles to cell therapies
setting up reliable consistent and scalable manufaturing system
cost effectiveness
ensuring therpies are safe and adequately regulated as well as ensuring the HCP knows how to use them
What is an ATMP
An advanced therapy medicinal product (ATMP) is a medicinal product which is either:
a gene therapy medicinal product
a somatic cell therapy medicinal product
a tissue engineered product
What does a MA ensure
quality, safety and efficay of all medicinal products
why might current regulatory frameworks be slowing progress of cell based therapeutic and why might this be a problem
they have been called outdated and fragmented. They time for the product to reach the market is slow and costly so it is argued that this is reducing their clinical impact. It can result in people finding loopholes to receive treatment and therefore cell tourism and receiving unproven therapies.
what are some key consierations around the regulation of these medicines
pharmacovigilence: detection, assessment, and undertanding to prevent adverse effects following market authorisation
good clinical practice: clinical trials to prove safety and efficacy, well defined scientific quality standards for design, conduct and recording of studies
clinical trials: prospectivley planned and appropriately controlled
describe holoclars route to market authourisation
- retrospective data was used from named patient treatments rather than performing a clinical trial with new patients. retrospective data is usually insufficient for regulatory approval
- evidence from 119 treatments was provided from a long term efficacy and safety study and 29 from an observational study
- the manufacturing process needed to be made compliant to GMP and converted to an industrial process to fit for commercial supply
