Regenerative Biology & Medicine Exam 1

Front 1

Can sensory & motor nerves regenerate? What are their limits?

Back 1

Yes, if the endoneurial tubes encasing the nerves remain intact and inregister at the site of injury. The ends of the axons on the proximal side of the injury are sealed off and their distal part degererates. The sealed proximal segment of the axon then sprouts an advancing growth cone, behind which the axon extends through the endoneurial tube to make new synapses with target skin and muscle.

Front 2

Mitotically competent cells?

Back 2

Cells that have the receptors and signal transduction pathways to respond to a regeneration-permissive environment

Front 3

What are the 3 pre-req’s needed for regeneration at the tissue level?

Back 3

1. Mitotically Competent Cells
2. Regeneration Promoting Signals Present: Injury environment must contain signals necessary to promote the proliferation and differentiation of the regenerative cells
3. Regeneration Inhibiting Signals Absent: suppressed or neutralized

Front 4

What are the three mechanisms of regeneration at the tissue level?

Back 4

Compensatory hyperplasia of differentiated cells

Activation of resident ASCs that self-renew within a specific micro niche

Creation of regeneration competent cells by dedifferentiation (amphibians & fish)

Front 5

Compensatory Hyperplasia

Back 5

Proliferation occurs while maintaining differentiated functions

Liver (Hepatocytes)
Pancreas


Example: liver

Front 6

Natural Regeneration via ASCs

Back 6

i. Resident undifferentatiated cells
ii. Self renewing, many divide asymmetrically
iii. 2 main types:
Epithelial stem cells
Mesodermal Stem Cells

Front 7

Erythrocytes need what for apoptosis?

*from book

Back 7

absence of erythropoietin

Front 8

what are "pro-life" signals & what do they do?

Back 8

GF, Cytokines, other Niche Factors

--> expression of BCL-2 on the outside of the Mito that protects/ stabilizes it

Front 9

this gene family is part of the "pro-life" gene family

Back 9

Bcl-2 family: Bcl-2 & Bcl-x

Front 10

Direct death signals (Reapers) are caused by?

Back 10

DNA damage
TNF-alpha
Hypoxia
Cell stress
Exercise to exhaustion

Front 11

Death signals cause increase?

Back 11

BAD, BAX

Front 12

what do BAD, BAX do?

Back 12

Destroys Bcl-2 --> destabilizes Mito membrane

Front 13

destabilization of Mito membrane leads to what?

Back 13

leakage of cytochrome c

Front 14

leakage of cytochrome c leads to what?

Back 14

activation of APAF-1 (Apoptotic Protease Activating Factor 1)

Front 15

What does APAF-1 do?

Back 15

activates Caspase-9

Front 16

What does capsase 9 do?

Back 16

activates caspase 3,7

--> digest cell

Front 17

walk through the cell death pathway

Back 17

Death Signals (TNF-alpha) increase Bad, Bax
1. BAD, BAX destroy Bcl-2 on Mito membrane
2. cytochrome c leaks & activates APAF-1
3. APAF-1 activates caspase-9
4. caspase-9 activates caspase-3,7 & digests cell

Front 18

life & death genes were first discoved in ?

Back 18

C. elegans

Front 19

What are the strategies of regenerative medicine?

Back 19

1. Cell Transplantation

2. Bioartificial Tissues

3. Induction of Regeneration In Situ

Front 20

Morphallaxis

Back 20

Hydra
regeneration of missing parts w/out growth -->
repatterning the remaining tissue into a proportioned but small whole, then growth

Front 21

Epimorphosis

Back 21

proliferation of stem or progenitor cells, followed by ther differntiation into the tissues that were lost

differentiation linked to growth

Front 22

Epimorphosis occurs in

Back 22

flatworms, annelid worms

amphibian appendages/jaw

deer antlers, rabbit ear tissue, fetal digits

Front 23

Pick up on stratagies of regen
3 Sep 2009

Back 23

3 sep 2009

Front 24

Fibroblasts synthesize 3 proteins in ECM

Back 24

Proteoglycan

Fiberous Proteins

Adhesive Proteins

Front 25

Proteoglycan

Back 25

part of ECM-Dermis

GAGs, bind HA & together trap water-> skin resists compression

Front 26

Fiberous Proteins: synthesized by Fibroblasts in the dermis

Back 26

a. Types 1 & 3 collagens, gives skin tensile strength
b. Collagen VI (six): stabilizes blood vesseles
c. Elastins: is stretchy, gives skin elasticity

Front 27

Adhesive proteins

Back 27

these provide a substrate for cell migration
a. Fibronectin
b. Tenascin
c. Vitronectin: associated w/elastins

Front 28

Skin Basement membrane is btw

Back 28

Stratum Basal of Epidermis & Papillary layer of Dermis

Front 29

3 basic phases of repair

Back 29

1. Hemostasis
2. Inflammaiton
3. Structural Repair

Front 30

Tissue Factor Pathway

Back 30

caused by 2nd Hemostasis
TF is a membrane spanning protein that initates cascad
1. TF:F7 --> activates F10
2. F10 cleaves F5 --> Prothrombin --> Thrombin

Front 31

Inflammation: What degrades the damaged collagen?

Back 31

MMP1,8
matrix metallo proteases

Front 32

Tissue Plasminogen Activator

Back 32

Angiogenesis:used by endothelial cell to get into wound

Converts Plasminogen ->Plasmin
Plasmin dissolves Fibrin

Front 33

What do fibroblasts do to get to wound

Back 33

secrete MMPs

Front 34

This will induce macrophage apoptosis

Back 34

VEGF
Vascular Endothelial Growth Factor

Front 35

causes the epidermis to thicken vertically by mitosis

Back 35

FGF7

produced by Fibroblasts

Front 36

what do fibroblasts do during Formation of granular tissue?

Back 36

Open up: MMP & HA

Fibronectin & Collagen1

FGF7 causing epidermis to proliferate

Front 37

lysyl oxidase

Back 37

causes Collagen1 to crosslink parallel with wound

Front 38

Remodel granular tissue into scar: this causes 'dieback'

Back 38

decreased EGF --> acellular fiberous pathc (scar

Front 39

Hemostasis: what do platelet secrete that causes Inflammation & re-epithelization ?

Back 39

TGF-beta
PDGF1,2,3

Front 40

during inflammation pithlia secrete this which causes proliferation

Back 40

EGF

Front 41

RTK ligands

Back 41

Used by the GF FGF, PDGF, EGF, VEGF, and SCF.

Front 42

macrophages secrete these during inflammation taht act on the Epi

Back 42

EGF, TGF-alpha, IL-1

Front 43

neutrophils secrete these during inflammation that act on Epi

Back 43

EGF, TGF-alpha, HGF

Front 44

Macrophages secrete these that affect fibroblasts during inflammation

Back 44

TGF-beta1,2: Migration

TGF-beta3 Proliferation

Front 45

Fetal skin, Unlike adult has these things that promote regen over fibrosis

Back 45

Low TGF-beta 1,2
High TGF-beta 3
trasiently IL-6

Front 46

nude mice that can regenerate have these signals

Back 46

High HA
Low: TGF-beta1,2; Collagen1

Front 47

macrophages & plateltes secrete these mitogenic factors for schwann cells

Back 47

FGF
PDGF
TGF-beta
IL-1,2,6
Inf-gamma

Front 48

chwann cells secrete these for neuron survival & elongation

Back 48

NGF
VDNF
NT3,4
CNTF
GDNF

Front 49

growth cone follows these adhesive factors from schwann cells

Back 49

N-CAM
N-CAD
L1
Ln, Fn

Front 50

NoGO pathway

Back 50

causes growth cone to collapse
ligand binds NoGo receptor
1. activates RhoA (exchagnes GDP for GTP)
Which leads to depolimerization of growth cone

Front 51

these activate NoGO receptor

Back 51

MAG
Olgiodendrocyte myelin
CSPGS
Ephrin B3
Tanacin R
NoGo

Front 52

4 major TF are always present in hepatocytes

Back 52

a) Liver specific form of NF2B (PHF)
b) STAT3: Signal Transducer & Activator of Transcription 3
c) AP-1
d) C/EBPβ

Front 53

• Delayed Early Genes

Back 53

activated during Progession phase of liver regen
1. CDK P-lates Rb
2. E2F disassociates from Rb
--> E2F drives cell into G1

Front 54

Liver regen needs 3 GF pathways

Back 54

1. HGF Pathway
2. EGF/TGF-alpha
3. TGF-alpha/IL6