MSK L22 Stem Cells Mo shariff Flashcards Preview

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Flashcards in MSK L22 Stem Cells Mo shariff Deck (22):
1

ESCs show

Pluripotency → Generate cells derived from all three embryonic cell types: endoderm, mesoderm, ectoderm

2

ESC's' Derived from

Inner cell mas of 4-5 day old blastocyst

3

Human embryonic germ cells derived from

5-10 week old foetus are also pluripotent

4

Adult Stem Cells: Definition

Undifferentiated cell found among differentiated cells in a tissue/organ that can renew itself, and differentiate to yield specialised clel types

5

Adult Stem Cells:Primary role

Is to maintain and repair the tissue in which they are found

6

Adult Stem Cells: Origin in mature tissues

Unknown but they exist in many tissues

7

Haematopoietic and mesenchymal cell differentiation:

Step 1: Haemopoeitic stem cell forms a multipotential stem cell
Two lineages:
1. Lymphoid progenitor cells
a. Production of immune cells
2. Myeloid precursor
a. Productino of neutrophils, eosinophils, blood cells etc.

8

Stromal cells →

1. Osteoblasts
2. Osteocytes
3. Chondroblasts

9


Adult Stem Cells:

1. Adult stem cells typically generate cell types of tissue in which they reside
2. Recent experiments indicate stem cells from one tissue can give rise to cells of a completely different tissue = PLASTICITY
a. Haemopoitic stem cells → neurones or muscle
b. Liver cells → made to produce insulin

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Trans differentiation →

adult stem cell genetically engineered to behave as embryonic stem cell

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ESC characteristics

Pluripotent
Large numbers
Easy to grow in culture

12

ASC characteristics

o Generally limitied to differentiation into cell types of their tissue origin n.b. evidence of plasticity
o Rare 00> identification and culture methods need
o Own patients cells therefore no rejection

13

Haemopoitic

1. Continuously renewing stem cells
2. Continuously formed
3. Fluid phase
4. Short-lived
5. Simple structures (unicellular, matrix-free)
6. Inflexible phenotype – little plasticity

14

Mesenchymal

o Stem cells (not necessarily continuously renewing)
o Formed at certain times
o Solid phase
o Long-lived
o Complex structures (multicell, matrix-bound)
o Plastic phenotype

15

Multipotent Mesenchymal Stem Cells:
Produced from →

1. Bone
2. Cartilage
3. Adipose tissue
4. Fibrous tissue
5. Connective tissue

16


Identification of Adult Human MSCs →

1. Capable of self-renewal and extensive proliferation
2. Transplanted in vivo can create bone organ
3. Remarkable phenotypic plasticity
4. Differentiate into cells of tissues that are embryologically unrelated
5. Ethically non-controversial alternative to Embryonic Stem Cells
6. CFU-F and progeny not identifiable
7. Some antibodies available

17

Transitional steps in OB lineage:

1. Linear sequence → osteoprogenitor to preosteoblast to osteoblast, lining cells or osteocytes
2. Identification by specific products → e.g. matrix proteins and receptor expression
3. Osteoblasts defined by site on bone and ability to synthesize Collagen I, osteonectin, Osteopontin, Osteocalcin, Alkaline phosphatase

18

Panel of monoclonal antibodies →

1. Facilitate selection of autologous bone marrow stem cells
a. Improved understandin of mesenchymal cell lineages (ageing and disease)
b. Monitor effects of therapeutics and treatment regimes
2. Clinical applications
a. Utilise osteogenic potential of MSCs in reconstructing localised skeletal defects
b. Gene therapy with MSCs
c. Reconstitution some/all of skeletal system to cure systemic diseases of bone such as osteogenesis imperfect

19

Regulation of osteoblast differentiation:

1. BMps (quite a few)
2. Most potent factors is osteoblast differentiation and function at extracellular level
3. 15 BMPs cloned, several rhBMPs produced
4. Various membrers expressed during skeletogenesis
5. Osteoblasts express BMPs and receptors in bone formation

20

CBFA1/Runx2 →aiding in differentiation (KNOW THIS)

1. Core- binding factor (CBF) transcription factors
2. Strong expression at osteogenic sites implicate it as an essential TF in osteoblast differention

21

3. Cbfa1 -/- mice have

total lack of bone and retain partially calcified cartilaginous skeleton
a. Membranous bones of skull and endochondral bone in skeleton is lacking

22

4. Cnfa1 +/- →

Cleidocranial dysplasia syndrome (CCD)
a. Affects teeth, bone, ribs and cranium.
b. Underdevelopment of the bones above

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