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BIOM30001 - Frontiers in Biomedicine > Lecture 13 - Stem Cells & Tissue Engineering > Flashcards

Lecture 13 - Stem Cells & Tissue Engineering Flashcards

1
Q

List the principle properties of stem cells

A
  • Undifferentiated
  • Capable of self-renewal
  • Capable of differentiating into multiple cell types
  • High proliferative potentiate
  • Present in low numbers
  • Quiescent in niche
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2
Q

In general, what determines stem cell behaviour?

A

Microenvironment (niche)

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3
Q

What are the roles of the ECM?

A
  • Structural support
  • Cell-cell communication
  • Sequestration of GFs
  • Sequestration of signalling molecules
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4
Q

Describe the generalised structure of the ECM

A

Gel-forming molecules
• Hyaluronan
• Aggrecans
• Proteoglycans

Fibrous proteins
• Collagen
• Elastin

Adhesive proteins
• Laminin
• Fibronectin

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5
Q

What is interesting about the behaviour of equal cells in different ECMs?

A

Apparently equal cells behave differently depending on the microenvironment (i.e. ECM)

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6
Q

What do we do when tissues or organs fail?

What are the issues with these approaches?

What is a possible future approach?

A

Transplantation
• Requires human donors
• Organ rejection

Prostheses
• Provides structural support, but often limited function

Making tissue from scratch?

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7
Q

Define tissue engineering

How does this differ from regenerative medicine?

A

Tissue engineering:
Process of growing new tissues and organs for the maintenance / repair / improvement / replacement of damage, diseased or poorly functioning tissues or organs

Regenerative medicine:
Application of stem cells to regrow tissues and organs

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8
Q

Describe some of the pioneering tissue engineering studies

A

Epicel:

Dermal regeneration template

Apligraf:

Carticel:

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9
Q

Describe the spectrum of tissue complexity in terms of tissue engineering

A

Increasing engineering complexity:

  1. Flat tissue structures:
    • e.g. cornea
  2. Hollow structures
    • e.g. Trachea
  3. Hollow, viscus structure
    • e.g. Bladder
  4. Solid organs
    • e.g. Kidney
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10
Q

Describe how vasculature is a barrier to tissue engineering

A

The most successful tissue engineering attempts have been with skin and cartilage
• Cartilage is avascular
• Skin is thin enough for diffusion of nutrients

Tissues rely on vasculature for nutrients, O2, and removal of cellular waste products

Any tissue thicker than 400 μm must be vascularised

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11
Q

Describe what can be done to circumvent the vascularisation challenge

A

Provision of biochemical signals with transplant to stimulate endogenous angiogenesis and neovascularisation

( • Angiogenesis: new vessels from pre-existing
• Neovascularisation: new vessel in absence of pre-existing)

Biochemical signals:
• VEGF
• PDGF
• FGF

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12
Q

What are the three central components of tissue engineering?

A
  1. Soluble factors (Biomolecules)
  2. Scaffold (Biomaterials)
  3. Cells
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13
Q

Describe the various origins and features of cells that can be used for tissue engineering

A

Source:
• Autologous (from own body)
• Allogeneic (from another individual of same species)

Differentiated
or
Undifferentiated (stem cell)

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14
Q

How are cells selected for tissue engineering?

A

There is an algorithm:

Need immediately: Yes/No

Yes:
Large organs:
• Allogeneic adult SCs, ESCs
• Banked iPSCs

Small organ:
• Autologous adult SCs, allogeneic SCs

No:
Large organs:
• Autologous adult cells and iPSCs

Small organ:
• Autologous adult primary cells or SCs, iPSCs

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15
Q

Describe the signal molecules that are used in tissue engineering

A

Needed to influence tissue engineered constructs and guide differentiation

  • BMPs
  • FGF-2
  • VEGF
  • TGFB1

These factors can be incorporated into the ECM during scaffold fabrication

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16
Q

Describe Biomaterials used in tissue engineering

Outline the main features required of biomaterials

What functions do they carry out?

A

Three dimensional biomaterials

Designed to:
• Direct organisation, growth, and differentiation of cells
• Maintain space and provide structural support
• Provide biological and mechanical cues
• Support transplanted or endogenous cells to attach, survive, proliferate, and differentiate

Features:

  1. Must be ‘biocompatible’
  2. Biodegradable
    • Gradual degradation / remodelling
  3. Mimic native ECM
  4. Promote native ECM production
17
Q

What are the various types of scaffold that can be used?

A

Natural:
• Polypeptides and polysaccharides

Synthetic:
• Can modify degradation rate
• Can be reproducible manufactured with mechanical properties

18
Q

List some factors of biomaterials that confer different properties on engineered tissues

A
  • Porosity
  • Cell adhesion and biorecognition
  • Water content
  • Mechanical properties
  • Resorption and degradation
  • Haemostatic
19
Q

Describe decellularisation of tissues

How does it occur?

What does it leave behind?

A

This process sees the removal of all cells from an organ

How? :
• Mechanical, enzymatic and/or chemical treatment

Leaves behind acellular, naturally occurring ECM
• Collagen rich
• Mechanical properties of tissues are retained

20
Q

What are the benefits of use of decellularised tissue?

A

ECM is highly conserved across species and will therefore be tolerated across individuals

21
Q

What are the potential approaches for the use of decellularised organs?

A
  1. Xenogeneic scaffolds
  2. Allogeneic scaffolds
    • Only perfect organs used for transplant
    • Remained could be used for scaffolds
22
Q

Describe the use of Bioprinting in tissue engineering

A

*

23
Q

How does tissue engineering relate to metabolic syndrome?

A 
Much end-organ damage experienced in MS:
 • Diabetic neuropathy
 • Diabetic nephropathy
 • Diabetic retinopathy
 • Peripheral vascular disease
 • IHD
 • Stroke
 • Arthritis

These organs / tissues could potentially be engineered for transplantation

24
Q

Give an operational

A

Maintain tissues and organ integrity by sustaining life long production of mature, functional cells in the steady state and in response to occasional stress

25
Q

Compare proliferative potential and lineage restriction along the classical stem cell hierarchy

A

Undifferentiated stem cells at the top of the hierarchy have great proliferative potential and aren’t lineage restricted

As cells become increasingly differentiation, there is a reduction in proliferative potential and the cells become lineage restricted

26
Q

List some ways that the microenvironment tells stem cells how to behave

A

Cues:
• Soluble factors
• Cell-cell interactions
• ECM

BIOM30001 - Frontiers in Biomedicine (35 decks)

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