Molecular Therapy Flashcards
only totipotent cell
zygote
cells capable of forming all cells in the body except extraembryonic or placental cell
pluripotent cells: mesenchymal, endodermal, exodermal
cells that can differentiate into cells in a single cell lineage
multipotent (adult stem cells)
less potent cell lines with only few possible differentiation options available
oligopotent and unipotent
concerns about embryonic stem cells
- ethical issues due to source
- teratogenicity (accumulation of chromosomal mutations from multiple passages)
- chromosomally unstable = malignant transformation
how are escs obtained
from blastocyst or inner cell mass during 1st week of gestation
creating esc via somatic nuclear transfer
- remove nucleus of developing zygote and replace with adult donor cell
creating induced pluripotent stem cells
- inducing transcription factors from earlier stage
- uses protooncogenes
- less risk for tumor formation
function of mesenchymal stromal cells
- provide signals for growth and differentiation for resident stem cells (niches)
direct administration of mscs to target organ
- smaller number of cells needed
- dec immunogenicity
- invasive
- works via paracrine effect
systemic delivery homing of mscs
- via iv infusion
- provide immunomodulation
- less invasive with similar efficacy
- downside: pulmonary sequestration or in areas of inflammation (away from target organ)
stem cell therapy in cardiology
- engraftment approaches
- gene modification of existing scar tissue
effect of msc on mi
- decrease size of infarct
- improve myocyte contractility and lvef in porcine models (high doses)
- ecc shortening
stem cells in endo
hscs and mscs promote endogenous pancreatic islet cell regeneration (preserving or protecting islet cell)
types of cell based immunotherapy
- immune modulation with mscs
- cancer immunotherapy
principle of dendritic cell therapy
- isolate and grow patient dcs
- expose them to tumor antigen lysate = prime to cancer
- reintroduce dcs into patients
- combats hiding tumor cells by directly exposing antigens to immune system
example of dendritic cell therapy
- sipuleucel t
- for castration-resistant prostate ca
t/f cytokine induced killer cells require helper cell activation
false, they rely on activating and inhibiting receptors on targeted cells
principles of cik therapy
- expand and prime patient’s killer cells
- introduce with dct (more effective)
what are adoptive t cell therapies
- t cells that are genetically modified for specific effects
- car t cells
fda approved anti cd19 car t cell therapies
- tisgenlecleucel: b cell lymphoblastic leukemia
- axicabtagene ciloleucel: refractory large b cell lymphoma
principles of gene therapy
- gene transfer
- gene silencing
- gene/ome editing
considerations for viral system in regenerative medicine
- not harmful
- can target specific populations of cells
- can express long term if required
- transgene expression regulatable
- could target specific dna sequences within es cells
use of mirnas
- can target multiple rnas for degradation
- can identify cancers
- can be inhibited
mirnas can inhibit ___ causing ___
- inhibit d2 and d3 cyclin
- cell undergoes cell cycle arrest and activates cellular apoptosis pathways
principle of genome editing
- remove offending genetic component
- crispr/cas9
- only for single genes with high penetrance
example of inducible gene expression
- tet on/tet off inducible gene complexes (uses tetracycline)
t/f in tissue engineering, autologous cells are preferred to avoid rejection
true
cellular scaffold production using decellularization
read
cellular scaffold production using adaptable biomaterials
read
benefits of bioprinting
- more complex structural arrangements of cell in 3d
- uses biogels and piezoelectric inkjet printing process
t/f liposomes can cross the bb but are very sensitive and degrade quickly
true
principle of gold nanoparticles
- direct drugs to intended targets
- minimize exposure to drug
- lessen chemotherapeutic dose
principle of iron oxide nanoparticles
- magnetic and magnoelectric properties allow “payloads” to be directed to places they cannot reach
