Lecture 13 - Tissue Engineering: Introduction Flashcards
What is a stem cell?
Undifferentiated cell
capable of slf-renewal
ability to differentiate into multiple cell types
defined by operation: maintain tissue and organ integrity
Why is stem cell research important?
Basci biology - cell fate decisions
Development - tissue formation
Homeostasis - tissue maintanance and turnover
Understand how alterations to steady state can result in disase
Potential to use cells as therapeutically
What are the classic stem cell properties?
renerwal
High proliferative potential
clonal repopulations _ single cell can form multiple cell types
multip-lineage differentiation
present in low marrows - rare
Quiscent - dormant (in niches)
morphologically unidentifiable
In responce to que’s in the niche (microenvironment) - there is a triggering of..
proliferation - self renewal
then
differentiation - hrough transit amplifying progenitor cells which are intermediate cells that produce different types of mature cells
The more differentiated the cell is, the less..
proliferative potential
What types of niche’s are there?
Restrictive - telling cell to stay quiscent
Permissive - go ahead
factors affecting the microenvironment can be cellular or a-cellular
ECM is comprised of
a network of macromolecules that provide strucutral support, and signalling molecules
Distribution and composition of ECM in different tissues is unique
Seemingly equal cells can behave differently depending on…
the microenvironment to which they are introduced
What determines cell fate?
Clues from Ontogeny
Cell-cell interactions, matrix, soluble factors required proliferation and differentiation
repair mechanisms often follow
developmental pathways
What are the option atm for when tissues or organs fail?
Transplantation - human donors, organ rejection
Prostheses - requires replacement, provides structural support but often limited function
What is tissue engineering?
Growing new tissues and organs for the maintenance/repair/improvement/replacement of damaged, diseases, or poorly functioning tissues or organs
What is the signifance of tissue complexity in realtion to tissue engineering bascics?
INcreasing fucntional parameters, metabolic requireemnts, cellular interactios, inter-organ-complications
All these increase the engineering complexity
What are the current limitations of tissue engineering?
vasculature
any tissue thicker than 400um must be vascularised
How are we addressing the lack of vasculature?
provide biochemical signals within transplant to stimulate endogenous angiogenesis and vascularisaion
the generation of well distributed blood vessels WITHIN engineered tissue in vitro remains a major challenge
Autologous cells are…
from own body
Alloogeneic cell are..
from another individual or speciesn - good because you can have them ready to go, but could be an immune response
What are some of the tissue engineering questions that need answering?
How do we isolate, where from
How do we generate enough cells for transplantation
how do we guide cells to differentiate and maintain desired phenotypes
how do we deliver cells to correct location
If needed immediately what are the options for Large organ and small organ tissue engineering?
Large Organ - Allogeneic adult SCs, ESCs
Small organ - Autologous adult SCs, allogeneic SCs
If NOT needed immediately what are the options for Large organ and small organ tissue engineering?
Large Organ - Autologous adults cells and iPSCs
Small ogran - Autologous adult primary cells, iPSCs
tissue engneering constructs are also influences by the presence of soluble
tissue engneering constructs are also influences by the presence of soluble growth factors
What are some examples tissue engineering constructs are also influences by the presence of soluble growth factorsf signalling molecules that are critical in development of differentiation of cell types?
BMPs
FGF-2
VEGF
can now be incorporated into ECM during scaffold fabrication
What functions does a scaffold have to serve?
provides 3D strucutre
space and strucural support
biomechanical que’s
has to be biologically acceptive to body
degratable over time
should MIMIC the native ECM
promote the bodies production of ECM
What rate of ECM degradation is best?
the same as the rate of production of native ECM
What are some examples of scaffolds?
polypeptides
sythetic
can combine symthetic with ECM moietics
What factos give scaffolds different properties?
porosity (permeability) cell adhesion water content mechanical properties resorption and degradation Haemostatic?
Decellularised tissues can be used for what?
providing an acellular, naturally occuring 3D scaffold containing ECM
the mechanical properties of the tissue are retained
CM is highly conserved acros species and will therefore be ..
well tolerated across individuals
what is the main problem with Decellularised tissues ?
still need an intact organ to start with - supply/demand issues
Still an new area of investigation
Bio 3D printing is able to..
deposit cells in a really sophisticated fashion - can have alternating cell types for instance
