Lecture 13 - Stem Cellsand Tissue Engineering Flashcards Preview

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Flashcards in Lecture 13 - Stem Cellsand Tissue Engineering Deck (37):
1

What is a stem cell?

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

2

Function of stem cells

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

3

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

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

4

Clonal repopulation example

A single haematopoietic stem cell can regenerate bone marrow

5

Can haematopoietic stem cells be morphologically recognised?

No

6

Type of cells between undifferentiated stem cells and differentiated tissue cells

Transit amplifying progenitors

7

What decreases a stem cell's proliferative ability?

Lineage restriction

8

What determines stem cell behaviour?

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

9

A way to study how stem cells differnetiate

Ontogeny, development

10

What is tissue engineering?

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

11

Epicel

A layer of keratinocytes.
For wound healing

12

Apligraf

A collagen matrix with dermal fibroblasts in it.
For wound healing.

13

Dermal regeneration template

Collagen and chondroitin layer, for healing of large wounds.

14

Tissue-engineering skin wound-healing technologies

Epicel
Apligraf
Dermal regeneration template

15

What is carticel?

For repairing cartilage defects.
Periosteal patch sewn over damaged cartilage. Injected with cultured chondrocytes.

16

Tissues that are easiest to engineer

Flat tissue structures, such as skin or cornea

17

Tissues in ascending order of complexity to engineer

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

18

Major limiting factor in engineering of larger organs

Vasculature

19

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

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

20

Potential therapy for repairing damaged cartilage

Carticel

21

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

400 micrometers

22

Tissue thickness that oxygen can diffuse across

150-200 micrometers

23

Way around vascularisation challenge for engineered tissues

Provide biochemical signals to stimulate endogenous angiogenesis in grafted tissue

24

Where can cells to be engineered come from?

Autologous - From own body
Allogeneic - From another member of the same species

25

Pros and cons of autologous cells

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)

26

Pros and cons of allogeneic cells

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

27

Usual growth factors that affect stem cell differentiation

BMPs, FGF-2, VEGF, TGFb1

28

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

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

29

What make up ECM?

Normally polypeptides, polysaccharides

30

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

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

31

Decellularised tissues

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

32

Pros of decellularised tissues

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

33

Cons of decellularised tissues
1)
2)

1) Need an intact organ to decellularise
2) Need endothelialisation to avoid thrombosis of ECM

34

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

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

35

Possible method for constructing biological tissues

3D printing

36

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

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

37

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

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