Stem cells Flashcards
What is totipotent?
Capable of giving origin to a new individual (e.g. fertilised egg and first 4 cells produced by its division)
What is pluripotent?
Differentiate into almost all types of adult cell but not into foetal or adult animal (e.g. embryonic stem cells)
What is multipotent?
Gives rise to more than one type of specialist cell (e.g. adult mesenchymal stem cells)
What is oligopotent?
Able to differentiate into a few cell types (e.g. myeloid stem cells)
What is unipotent?
Able to differentiate into a single cell type
What are the major groups of stem cells (4)?
- Embryonic stem cells
- Induced pluripotent stem cells (iPS cells)
- Foetal tissue and umbilical cord stem cells
- Adult (somatic) stem cells
What are the different types of adult (somatic) stem cells (3)?
- Haemapoietic stem cells
- Bone marrow derived mesenchymal cells
- Mesenchymal cells
What are the different properties of stem cells?
- immature, non-specialised and able to differentiate within adult organisms
- capable of self renewal
- clongeneicity
- expression of verified stem cell markers
- can be induced experimentally to differentiate into various cell lineages
- Adult stem cells can be transplanted from one area and grow into a different type of tissue
What are the different types of dental stem cells (5)?
- Dental pulp stem cells (DPSCs)
- Stem cells from human exfoliated deciduous teeth (SHED)
- Periodontal ligament stem cells (PLSCs)
- Dental follicle stem cells (DFSCs)/ Dental follicle progenitor cells (DFPCs)
- Stem cells from the apical papilla (SCAP)
Which dental stem cells come from permanent teeth pre-eruption?
SCAPs, DPSCs, DFPCs, GSCs
Which dental stem cells come from permanent teeth after eruption?
PDLSCs, DPSCs
Which dental stem cells come from deciduous teeth before exfoliation?
DPSCs
Which dental stem cells come from deciduous teeth after exfoliation?
SHED
Which dental stem cells come from the tooth germ?
DFPCs
What are the potential dental applications for dental stem cells (5)?
- Pulpal regeneration in endodontics
- Periodontal regeneration including guided tissue regeneration
- Craniofacial regeneration
- Dental implantology - new bone formation
- Engineering of new teeth (bio teeth)
What are some of the potential medical applications for dental stem cells (6)?
- Treatment for liver disease
- Muscular dystrophy
- Stroke
- Diabetes
- Spinal cord regeneration
- Cardiac repair
Tell me more about dental pulp stem cells (DPSCs):
- Found in a quiescent state in healthy pulp but source of odontoblasts to form tertiary dentine,
- Experimentally:
- found to produce tubules similar to dentine,
- forms pulp-dentine like complex (without epithelial-mesenchymal interactions),
- less good osteogenesis,
- but shown to be adipogenic, neurogenic, chondrogenic and myogenic in vitro
Tell me more about stem cells from exfoliated deciduous human teeth (SHED):
- High rate of proliferation
- Osteogenic, adipogenic, neurogenic, myogenic and chondrogenic in vitro
- regenerate pulp like complex (but not dentine-pulp complex) in vivo
- repair bone defects in mice
Tell me more about periodontal ligament stem cells (PDLSCs):
- Homeostasis and regeneration of periodontal tissues or defects (prevents ankylosis)
- Differentiates to form cementoblasts, osteoblasts and fibroblasts
- Experimentally:
- forms fibroblasts
- osteogenic, cementogenic, adipogenic, neuronal precursors
- potential to regenerate PDL in people with perio
- cementum/PDL like complex -> dense collagen type 1 with sharpey like fibres embedded into cementum in vivo
- expanded tem cells on 3D scaffolds = bone formation
Tell me more about dental follicle stem cells (DFSCs)/Dental follicle precursor cells (DFPCs):
- Dental follicle = precursors for PDL, cementum and bone
- Source from impacted 3rd molars - can be cryopreserved
- Potential tissue engineering application (complete peridontium) but not observed in vivo yet
- cementogenic, adipogenic, neurogenic and osteogenic in rats at ectopic sites
- characteristics vary across species studied
Tell me more about Stem cells from the apical papilla (SCAP):
Apical papilla = soft tissue at apices of developing permanent teeth
- source of primary odontoblasts for development of root dentine
- Experimentally:
- high proliferative potential
- forms odontoblast-like cells and produce dentine in vivo
- adipogenic and neural cell markers
- Possibly the best source for root dentine formation
Why is isolation of stem cells challenging?
- Identification of the niche where they reside and are able to retain their “stemness” not fully understood
- Lack of specific markers
- Large number needed for stem cell replacement therapy (in vitro expansion)
- Needs growth factors and or extracellular matrix components to stop differentiation
What do stem cell markers CD146 and STRO-1 suggest about location of DPSCs?
Located in perivascular and perineural sheath regions
Where are most stem cells found?
Around blood vessels (n.b. not in all tissues)
Where are PDLSCs and SCAP?
In perivascular regions with additional scattered clusters
What is tissue engineering?
Describes the process by which tissues and organs are regenerated by stem cell transplantation with and without a scaffold to reconstruct and restore the function of damaged or diseased tissues and organs
What is organ replacement therapy?
Has great potential for the replacement of dysfunctional organs via a regenerative strategy of the whole organ by reconstructing a fully functional bioengineered organ using 3D cell manipulation in vitro
What are the current treatment options for periodontal disease?
- disease control intervention
- bone or hydroxyapatite grafts
- guided tissue regeneration using barrier membranes
- use of growth factors and host-modulating agent
What are the 5 important factors to be achieved for successfully periodontal regeneration?
- functional epithelial seal must form
- new acellular cementum must be generated on the root surface
- alveolar bone must be restored
- new sharpey fibres must insert into cementum and alveolar bone
- gingival connective tissue must reform
What is the current method used for periodontal regeneration?
- isolation of PDLSCs and expand in vitro
- transplant expanded PDLSCs into animal models with surgically created periodontal defects
- hydroxyapatite/tricalcium phosphate career used
- regeneration of cementum and PDL like structures observed
What does regeneration of dentine rely upon?
Vital pulp
What have the difficulties in dentine/pulp regeneration been so far?
Difficulties with revascularisation
What is hydrogel?
A scaffold material that has been developed -> poured into a pulp chamber and self polymerises under physiological conditions to form a solid gel capable of supporting cell growth and differentiation
What may be the alternative to regenerating a whole tooth?
Regenerating a root e.g. using DFSCs -> then place a crown on it (experiments have shown this to be successful)
Which cells can be used for tooth regeneration?
DPSCs, SHED and SCAP reprogrammed into iPS (similar properties to embryonic stem cells = produce epithelial cell line e.g. ameloblasts)
How does whole tooth regeneration work?
Bioengineer a tooth germ = transplanted directed into alveolar bone socket or grown in vitro and transplant tooth
What problems have been found in a paper trying to regenerate a tooth?
Tooth generated was too small
What are the potential problems and issues for tooth regeneration (11)?
- Identification, maintenance and expansion of stem cells
- Formation of iPS cells
- Controll of tooth size and shape
- Controllable bio-tooth growth and eruption
- Availability of odontogenic epithelium
- Pulp re-vascularisation and neural regeneration
- Host-graft immunorejection
- understanding the immunogenicity and immunoregulatory properties of the stem cells
- Design of appropriate delivery devices
- Cost-benefit/effectiveness
- Time for treatment
