Lecture 13 - Stem Cellsand Tissue Engineering

Question 1

What is a stem cell?

Answer 1

Undifferentiated cell capable of self-renewal. Can differentiate into multiple cell types.

Question 2

Function of stem cells

Answer 2

Maintain tissue and organ integrity by maintaining life-long production of mature, functional cells in steady state, and in response to stress

Question 3

Classic stem cell properties
1)
2)
3)
4)
5)
6)

Answer 3

1) Renewal
2) High proliferative potential
3) Clonal repopulation
4) Multi-lineage differentiation
5) Present in low numbers
6) Quiescent in niche

Question 4

Clonal repopulation example

Answer 4

A single haematopoietic stem cell can regenerate bone marrow

Question 5

Can haematopoietic stem cells be morphologically recognised?

Answer 5

No

Question 6

Type of cells between undifferentiated stem cells and differentiated tissue cells

Answer 6

Transit amplifying progenitors

Question 7

What decreases a stem cell’s proliferative ability?

Answer 7

Lineage restriction

Question 8

What determines stem cell behaviour?

Answer 8

Factors secreted by stromal cells, progenitor cells, soluble factors.
ECM composition

Question 9

A way to study how stem cells differnetiate

Answer 9

Ontogeny, development

Question 10

What is tissue engineering?

Answer 10

Process of growing new tissues and organs for the replacement, repair, improvement of damaged, diseased, poorly-functioning organs.

Question 11

Epicel

Answer 11

A layer of keratinocytes.

For wound healing

Question 12

Apligraf

Answer 12

A collagen matrix with dermal fibroblasts in it.

For wound healing.

Question 13

Dermal regeneration template

Answer 13

Collagen and chondroitin layer, for healing of large wounds.

Question 14

Tissue-engineering skin wound-healing technologies

Answer 14

Epicel
Apligraf
Dermal regeneration template

Question 15

What is carticel?

Answer 15

For repairing cartilage defects.

Periosteal patch sewn over damaged cartilage. Injected with cultured chondrocytes.

Question 16

Tissues that are easiest to engineer

Answer 16

Flat tissue structures, such as skin or cornea

Question 17

Tissues in ascending order of complexity to engineer

Answer 17

Flat tissues
Hollow structures
Hollow, viscous structures (EG: bladder)
Solid organs

Question 18

Major limiting factor in engineering of larger organs

Answer 18

Vasculature

Question 19

Why have attempts to engineer skin and cartilage been more successful than other tissues?

Answer 19

They are less dependent on blood supply.
Cartilage is avascular.
Skin is thin enough for diffusion

Question 20

Potential therapy for repairing damaged cartilage

Answer 20

Carticel

Question 21

How thick must a tissue be in order to require vascularisation?

Answer 21

400 micrometers

Question 22

Tissue thickness that oxygen can diffuse across

Answer 22

150-200 micrometers

Question 23

Way around vascularisation challenge for engineered tissues

Answer 23

Provide biochemical signals to stimulate endogenous angiogenesis in grafted tissue

Question 24

Where can cells to be engineered come from?

Answer 24

Autologous - From own body

Allogeneic - From another member of the same species

Question 25

Pros and cons of autologous cells

Answer 25

No immune rejection
Need a lot of cells to make a large organ (invasive)
Slower process than using banked allogeneic cells (mightn’t be as useful for emergencies)

Question 26

Pros and cons of allogeneic cells

Answer 26

Can use banked cells from a healthy individual
Might be rejected by the immune system
Could transmit diseases

Question 27

Usual growth factors that affect stem cell differentiation

Answer 27

BMPs, FGF-2, VEGF, TGFb1

Question 28

Necessary properties for engineered ECM
1)
2)
3)
4)

Answer 28

1) Biocompatible to person receiving ECM
2) Biodegradable (will slowly degrade/be remodelled in body)
3) Support transplanted or endogenous cells
4) Mimic, promote growth of endogenous ECM

Question 29

What make up ECM?

Answer 29

Normally polypeptides, polysaccharides

Question 30

Factors that give ECM different properties
1)
2)
3)
4)
5)

Answer 30

1) Permeability
2) Cell adhesion, biorecognition
3) Water content
4) Mechanical properties
5) Reabsorption, degradation rate

Question 31

Decellularised tissues

Answer 31

Remove cells from an organ via a series of mechanical, enzymatic and chemical treatments.

Question 32

Pros of decellularised tissues

Answer 32

1) Provides an acellular, 3D protein scaffold of an organ.
2) Topology and ECM profile most closely support recapitulation of organ, revascularisation, integration with surrounding tissues.
3) Can be seeded with stem cells from host. Transplantation.
4) ECM is highly conserved between species

Question 33

Cons of decellularised tissues
1)
2)

Answer 33

1) Need an intact organ to decellularise

2) Need endothelialisation to avoid thrombosis of ECM

Question 34

Where could organs for decellularisation be obtained?
1)
2)

Answer 34

1) Xenogenic

2) Allogenic organ donation. Perfect organs used for transplant, rest used for scaffolds

Question 35

Possible method for constructing biological tissues

Answer 35

3D printing

Question 36

Advantages of 3D printing of biological tissues
1)
2)
3)
4)

Answer 36

1) Precise control of architecture
2) Control density, functionality, shape to mimic organs
3) Controlled gradients in mechanical properties
4) Controlled gradients of biologically-active factors

Question 37

Stem cell therapies for metabolic syndrome complications currently being investigated
1)
2)
3)
4)
5)
6)
7)

Answer 37

1) Diabetic neuropathy
2) Diabetic nephropathy
3) Diabetic retinopathy
4) Peripheral vascular disease
5) Ischaemic heart disease
6) Stroke
7) Arthritis