Stem cells Flashcards
What is a stem cell?
-A stem cell can self renew to maintain the stem cell pool
-they can differentiate into specialised cells by the switching on of specific genes due to internal/external chemical signals.
-stem cells are produced to replace damaged cells.
what are the 3 different types of stem cells?
-totipotent stem cells - these can differentiate into any cell type and can give rise to an entire organism
(zygote)
-pluripotent stem cells - can differentiate into almost any cell type, excluding those found in the placenta. they are derived from the inner mass of blastocysts and can develop into any of the three germ layers (ectoderm-skin, CNS, PNS, mesoderm-muscles, skeletal system, blood, kidneys and endoderm-digestive and respiratory tract linings, liver,pancreas)
-multipotent stem cell- they can differentiate into limited range of cell types within the body. For example, hemopoietic stem cells can differentiate into different blood cells but not into any other tissues. aids in the regeneration of certain tissues. derived from stem cell niche
what are the 3 types of stem cells that are relevant to therapy and provide information on how these are obtained as well as their advantages and diasadvantages?
Embryonic stem cell -
They are pluripotent and the can differentiate into any cell type excluding those of the placenta ta=hat is required to support and grow fetes in the womb. Derived from inner mass of blastocysts.can be used for regenerative medicine
+high pluripotent therefor can differentiate into many cell types
+unlimited growth therefore provides good resources for research and therapeutic use.
-risk of rejection by recipients immune system
-tumor growth development risk due to high pluripotent
-derived from embryo therefor raises ethical concerns as it involves destroying embryo
Adult stem cells-
They are multipoint, differentiating into limited number of cell types like heamatopoetic stem cells, developing into different blood cells, can be used fr conditions like leukaemia and other blood disorders.
+low risk of immune system rejection as it works by using patients own cells/genetic material.
+not ethically problematic as it is derived from patients own cells
-unlimited growth (hard to grow and isolate in culture)
-Limited differentiation therefore limits application in regenerative medicine)
IPSC-
They are reprogrammed in lab to express certain genes and factors to return to embryonic-like pluripotent state and differentiate into many cells types
+address ethical concerns associated with ESC as it docent require embryos
+reduce risk of immune rejection as it uses patients own cells
+application to regenerative medicine
-changing adult cells to stem cells may cause them to act differently or increase risk of cancer development
-complex and costly limiting accessibility for widespread clinical use.
what are allogeneic and autologous stem cells and what are the advantages and disadvantages of these stem cells?
allogeneic stem cells: these are the donor cells that include ECS, IPSCs and adult stem cells.
advantages: wide availablilty as it can be derviced from healthy donors to treat conditions without need to harvast patient-derived cells
disadvantage: risk of immune rejection by recipent immune system which can recognise those cells as foreign
autologous stem cells: these are the the patients own stem cell which have been harvassed (bone marrow or fat tissue), processed then re introduced.
advantages: no immunological compatibility needed/no HLA matching.
and lower risk of immune rejection
disadvantage: high costs associated with single preparation for each patient. more time consuming and constly to harvast it, process it then re introduce it.
what are neural stem cells?
these are adult stem cells that are multipotent and can differentiate into neural and glial progenitors and they can then differentiate into mature neurons and glial cells.
they are found in the central canal of the spinal cord.
sub ventricular zone and subgranular zone.
what is adult neurogenesis?
Neurogenesis is the ability of the CNS to generate new neurons in adulthood.
Influenced by many factors like diet exercise stress learning.
Neural stem cells –> neural progenitor cells–> promotes migration to the site of injury they can differentiate into mature neurons.
They can then integrate into the circuity of the brain.
however this is not enough for major injuries/damages as neurogenesis in adulthood occurs in restricted regions limited to only in the SVZ and the SGZ, therfore limited migration to other sites of damage. and the number of neurones generated in adulthood neurogenesis is relatively small, if damage is relaly bad then its exceeds the number of nuerones the brian can regenerate. rate of neurodegeneration decreases wirh age
adultneurogenesis occurs in two places: the subventricular zone - lining the lateral ventricles and the subgrandular zone of the dentate hippocampus.
what is neurogenesis?
this is the regrowth and repair of nervous system tissues or cells through the use of stem cells.
stem cells can secrete angiogenic factors for the formation of CNS blood vessels, secretion of anti-inflammatory factors for immunomodulation such as reducing macrophage infiltration and microglia activation. they can also allow for synapse formation and neurogenesis (the formation of neuronal and glial cells).
what are some of the factors that need to be taken into account with stem cell therapy?
-the stage of the disease of the patient.
-what stem cell is being used (ESCs or IPSCS, or adult)
-tissue source - bone marrow and umbilical cord.
-maintenance of genetic stability
-route of delivery - intravenous or intranasal?
-decide when to collect results
-how to measure cell function (biomarkers, qol, imaging)
what are the 2 types of spinal cord injury and the different items of injury?
complete - no function/feeling below the site of injury
incomplete - some function/feeling below the site of injury
C4-C6 - tetraplegia
T6- paraplegia
L1- paraplegia
sacral - impaired bowel/bladder control
what is the pathology of spinal cord injury and include the 3 different phases
primary injury: vascular disruption, haemorrhage and severed axons
acute phase 0-48 hours: infiltration of activated macrophages and astrocytes-typeof glial cell that support neural enviroment and function, oedema and inflammation
chronic phase 2 weeks to 6 months: severed and demyelinated axons.
what tool is used to measure improvement in spinal cord injury and how many levels of improvement are associated with increased qol?
the upper extremity motor scale
2 level improvement is associated with qol.
OPC1 stem cell therapy for spinal cord injury:
describe the mechanim of action, preclinical studies, clinical trials, analysis of score at the end and current status.
They have developed ologodendorcyte progenitor cell line called OPC1.
Took a single unused embryo and developed an oligodendrocyte progenitor cell line and produced a cell bank(storage of cells for future use).
Rationale for this: they argue that injection of this into the lesion can bring back differentiation into oligodendrocytes and these can remyelinate the axons and can restore axons conductivity.
Suggested that they can also secrete neutrophic factors and seceret angiogeneic factors.
This will prevent cavitation of the spinal cord and improve qol
preclinical studies:
mouse: they used a shivever mouse that has a deficiency in the myelin basic protein. untreated vs treated, the treated mice showed that the progenitor cells were wrapped around the host neurons and this formed compact myelin sheath.
rats: they used rats with thoracic spinal cord injury. Cavity site was significantly reduced in size and the it was found that the myelinated axons did extend across the cavity.
clinical trial:
-Selected patients that had injury c4-c7
-5 cohorts with different doses.
-Cohort 1, 2 and 3, had complete injury so had no functional sensation below the injury site.
-4 and 5 – had incomplete they had some sensation below site of injury.
-Escalated dose from one cohort to the next once no safety issues were found.
-Treatment window – 14-30 days post injury, injected into spinal cord region.
-40-60- gave immunosuppression.
-Primary assessment – valuate safety and then see if they had a change in the upper extremity motor score from baseline.
-Followed them up at 1,2,3,6 and 12 months.
results:
Safety profile: all participants experienced at least one adverse event. Only 32 of 534 therapy-related. Others related to SCI complications
Efficacy: 21/22 of patients attained at least 1-motor-level improvement majority of patients showed improvements in sensory scores
No correlation between the level of improvement & cell dose or time of intervention
Current status: device that will permit a precise administration without stopping the patient’s ventilator under investigation
