Lecture 16 - Stem Cells in the Lung Flashcards Preview

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Flashcards in Lecture 16 - Stem Cells in the Lung Deck (47):
1

From which germ layer does the lung epithelium arise?

Endoderm

2

From which germ layer does the innervation of the lung arise from?

Ectoderm (neural crest cells)

3

From which germ layer does the endothelium, haematopoietic cells and lung mesenchyme arise from?

Mesoderm

4

Which part of the lung arises from the endoderm?

Lung epithelium

5

Which part of the lung arises from the ectoderm?

Innervation

6

Which part of the lung arises from the mesoderm

Lung endothelium, mesenchyme and haematopoietic cells

7

Number of different cell types in the lung

Over 50

8

How is the lung epithelium formed?

A proliferation of an endodermal progenitor in the foregut endoderm.

9

How are the conducting and respiratory airways formed?

Branching morphogenesis

10

How are the lungs developed?
1)
2)
3)
4)

1) Endodermal progenitor proliferates in the foregut endoderm, forming the lung epithelium.
2) Epithelial lung bud forms surrounded by loosely-packed mesenchymal cells.
3) Branching morphogenesis forms conducting and respiratory airways
4) Alveologenesis forms alveoli

11

Stages of lung development
1)
2)
3)
4)
5)

1) Embryonic
2) Pseudoglandular
3) Canalicular
4) Sacular
5) Alveolar

12

When does surfactant start to be produced?

Sacular period (around week 25)

13

Where are lung epithelial stem cells located during embryonic development?

At the distal tip of the growing lung bud

14

How can you stain for embryonic epithelial lung stem cells?

LD2 expression.

15

Which type of stem cell are lung epithelial stem cells?

Multipotent

16

Which cell type can give rise to goblet cells and ciliated cells?

Club cells

17

Cell types that club cells give rise to

Goblet cells and ciliated cells

18

Which part of the mesoderm do mesenchymal cells arise from?

Splanchnic mesoderm

19

What do mesenchymal cells give rise to in the lung?

Fibroblasts and smooth muscle cells

20

Expression of what marks mesenchymal progenitor cells in the lung?

FGF-10 expression

21

What does LD2 expression mark?

Lung epithelial stem cells

22

What does FGF-10 expression mark?

Mesenchymal stem cells

23

Role of FGF-10

Epithelial progenitors grow towards FGF-10 (FGF-10 secreted by mesenchymal progenitors at the tip of the lung bud, driving formation of bud).

24

What does the lung vasculature develop from?

Endothelial progenitor cells of the mesoderm

25

Why do the heart and lungs often have comorbidities?

Because they share a stem cell line (multipotent cardiopulmonary progenitor)

26

How to use flow cytometry to analyse lung stem cells
1)
2)

1) Digest lungs with collagenase
2) Colony-forming assay

27

Rationale behind a colony-forming assay

Stem cells will be able to regenerate. More-differentiated cells won't be able to do so.

28

Phenotype of lung epithelial progenitor cell

CD45 negative
CD31 negative
EpCAM positive
CD24 low

29

How are lung epithelial progenitor cells grown in culture?

As a co-culture with lung stromal cells

30

Three colony types of colony-forming assay of lung cells

1) Airway
2) Alveolar
3) Mixed

31

How are alveolar cells identified in a colony-forming assay?

Expression of Pro-spc (surfactant)

32

How are airway cells identified in a colony-forming assay?

Muc-ac expression (mucin)

33

What is the significance of finding alveolar, airway and mixed colonies in a colony-forming assay?

There are cells in the lungs that are committed to one lineage (alveolar or airway) and cells that are multipotent.

Airway colonies can only give rise to airway colonies.
Alveolar colonies can only give rise to alveolar colonies.

34

How was the lung epithelial stem cell nice found?
1)
2)
3)

1) Club cells are depleted by naphthaline.
2) Naphthaline used to deplete club cells of airways. After ~3 days club cells were regenerated.
3) Location of regeneration found using histology

35

What determines epithelial stem cell fate?

Microenvironment (supported by stromal cells)

36

Lineage specifications of mesenchymal cells
1)
2)

Three distinct types found using flow cytometry:
1) CD166+ has low proliferative capacity, becomes myofibroblasts.
2) Two CD166- types are multipotent, can become either myofibroblasts or lipofibroblasts

37

Factor released by mesenchymal stromal cells in the lung that allow epithelial stem cells to regenerate

FGF-10

38

Most important expressed molecules that allow identification of adult lung epithelial stem cells

Differential expression of EpCAM and CD24

39

Another name for culture-forming assay

In vitro clonogenic assay

40

Which rank do lung diseases have worldwide for disease prevalence and cost?

2nd

41

When might a stem-cell therapy for lung disease a good idea?

When the disease is chronic. If it is acute, stem-cell therapy might be too slow

42

Two main approaches for stem cell therapy

1) Deliver functioning stem cells to needed area
2) Deliver factors that will result in genesis of stem cells in needed area

43

Why aren't embryonic stem cells appropriate for transplant?

Form teratomas

44

For what could stem cells be used as a gene therapy?

Cystic fibrosis

45

Successful tissue decellularisation transplant

Trachaea

46

Problem with tissue decellularisation

Organ being made must be self-renewing. Need to understand how cells communicate in tissue

47

Another role of mesenchymal stem cells

Intrinsically anti-inflammatory