Lecture 13 - Tissue Engineering: Introduction

Question 1

What is a stem cell?

Answer 1

Undifferentiated cell
capable of slf-renewal

ability to differentiate into multiple cell types

defined by operation: maintain tissue and organ integrity

Question 2

Why is stem cell research important?

Answer 2

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

Question 3

What are the classic stem cell properties?

Answer 3

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

Question 4

In responce to que’s in the niche (microenvironment) - there is a triggering of..

Answer 4

proliferation - self renewal

then

differentiation - hrough transit amplifying progenitor cells which are intermediate cells that produce different types of mature cells

Question 5

The more differentiated the cell is, the less..

Answer 5

proliferative potential

Question 6

What types of niche’s are there?

Answer 6

Restrictive - telling cell to stay quiscent

Permissive - go ahead

factors affecting the microenvironment can be cellular or a-cellular

Question 7

ECM is comprised of

Answer 7

a network of macromolecules that provide strucutral support, and signalling molecules

Distribution and composition of ECM in different tissues is unique

Question 8

Seemingly equal cells can behave differently depending on…

Answer 8

the microenvironment to which they are introduced

Question 9

What determines cell fate?

Answer 9

Clues from Ontogeny

Cell-cell interactions, matrix, soluble factors required proliferation and differentiation

Question 10

repair mechanisms often follow

Answer 10

developmental pathways

Question 11

What are the option atm for when tissues or organs fail?

Answer 11

Transplantation - human donors, organ rejection

Prostheses - requires replacement, provides structural support but often limited function

Question 12

What is tissue engineering?

Answer 12

Growing new tissues and organs for the maintenance/repair/improvement/replacement of damaged, diseases, or poorly functioning tissues or organs

Question 13

What is the signifance of tissue complexity in realtion to tissue engineering bascics?

Answer 13

INcreasing fucntional parameters, metabolic requireemnts, cellular interactios, inter-organ-complications

All these increase the engineering complexity

Question 14

What are the current limitations of tissue engineering?

Answer 14

vasculature

any tissue thicker than 400um must be vascularised

Question 15

How are we addressing the lack of vasculature?

Answer 15

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

Question 16

Autologous cells are…

Answer 16

from own body

Question 17

Alloogeneic cell are..

Answer 17

from another individual or speciesn - good because you can have them ready to go, but could be an immune response

Question 18

What are some of the tissue engineering questions that need answering?

Answer 18

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

Question 19

If needed immediately what are the options for Large organ and small organ tissue engineering?

Answer 19

Large Organ - Allogeneic adult SCs, ESCs

Small organ - Autologous adult SCs, allogeneic SCs

Question 20

If NOT needed immediately what are the options for Large organ and small organ tissue engineering?

Answer 20

Large Organ - Autologous adults cells and iPSCs

Small ogran - Autologous adult primary cells, iPSCs

Question 21

tissue engneering constructs are also influences by the presence of soluble

Answer 21

tissue engneering constructs are also influences by the presence of soluble growth factors

Question 22

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?

Answer 22

BMPs
FGF-2
VEGF

can now be incorporated into ECM during scaffold fabrication

Question 23

What functions does a scaffold have to serve?

Answer 23

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

Question 24

What rate of ECM degradation is best?

Answer 24

the same as the rate of production of native ECM

Question 25

What are some examples of scaffolds?

Answer 25

polypeptides

sythetic

can combine symthetic with ECM moietics

Question 26

What factos give scaffolds different properties?

Answer 26

porosity (permeability)
cell adhesion
water content
mechanical properties
resorption and degradation
Haemostatic?

Question 27

Decellularised tissues can be used for what?

Answer 27

providing an acellular, naturally occuring 3D scaffold containing ECM

the mechanical properties of the tissue are retained

Question 28

CM is highly conserved acros species and will therefore be ..

Answer 28

well tolerated across individuals

Question 29

what is the main problem with Decellularised tissues ?

Answer 29

still need an intact organ to start with - supply/demand issues

Still an new area of investigation

Question 30

Bio 3D printing is able to..

Answer 30

deposit cells in a really sophisticated fashion - can have alternating cell types for instance