Flashcards in Ch3:Tissue Renewal, Regeneration, and Repair Deck (102):
Two parts of tissue renewal?
What is regeneration?
Complete restitution of lost or damage tissue through proliferation of cells and tissues
What is the requirement for regeneration to occur?
Stem cells of tissues are not destroyed
What is repair?
Restoration of original structures but can be structurally deranged.
What does repair consist of?
Combination of regeneration and scar formation by the deposition of collagen
What is the predominant healing process that occurs when the extracellular matrix framework is damaged?
What is fibrosis?
Extensive deposition of collagen
Damage to the matrix (parenchymal stem cell matrix) results in what? 2
2. Scar formation
The size of cell population is determined by what? (3)
1. Cell proliferation
2. Cell differentiation
3. Death by apoptosis
Cells incapable of replication are known as what?
Terminally differentiated cells
Proliferation of cells can be stimulated by what two types of conditions?
What is epithelium?
What is mucosa?
Epithelium that absorbs and is moist
What are continuously dividing tissues called?
Examples of continuously dividing cells? 3
2. Hematopoietic cells
3. Mature cells derived from adult stem cells
What are quiescent tissues called?
Level of replication in quiescent?
When can it speed up?
In response to stimuli
Examples of quiescent cells? 3
1. Parenchymal cells of liver, kidney, pancreas
2. Mesenchymal cells
3. Vascular endothelium
Nondividing tissues are known as what?
Examples of permanent tissue? (3)
1. Neural tissue
2. Skeletal muscle
3. cardiac muscle
What is regenerative medicine?
Repairing damaged human tissues through stem cells
What makes stem cells so intriguing for repair? 2
1. Self-renewal properties
2. Capacity to generate differentiated cell lineages.
How is the replication of stem cells described?
Obligatory asymmetric replication
What is obligatory asymmetric replication?
Each stem cell division, one of the daughter cells retains its self-renewing capacity while the other enters differentiation pathway
How is the ratio of stem cells/differentiated cells described?
What is stochastic differentiation?
Population if maintained by the balance between stem cells divisions that generate either two self-renewing stem cells or two cell that will differentiate
Stem cells that can generate all tissues of the body are known as what?
Examples of pluripotent cells? 2
Induced pluripotent stem cells (iPS)
Where do adult stem cells reside?
What makes up a niche?
Mesenchymal, endothelial, and other cell types
Niche cells do what?
Generate or transmit stimuli that regulate stem cell self-renewal and generationi of progeny cells
Embryonic stem cells are found where?
Inner cell mass of blastocysts in early embryonic development
Research applications of embryonic stem cells? 3
1. Study specific signals and differentiation steps required for a tissue
2. Production of knockout or knockin mice
3. Repopulate damaged organs
Result of reprogramming differentiated cells?
Induced pluripotent stem cells
What is reproductive cloning?
Transfer of nuclear material into oocyte
How effective is therapeutic and reproductive cloning?
Deficiency in histone methylation results in improper gene expression
What does the pluripotency of cells in a clone depend on?
Expression of four transcription factors known as oncogenes
What are transit amplifyin cells?
Rapidly dividing cells generated from somatic stem cells
What is transdifferentiation?
Change in the differentiation of a cell from one type to another
What is special about hemopoietic stem cells?
Can differentiate into hepatocytes and neurons upon fusion with already differentiated cells of target tissue
What is developmental plasticity?
Ability of cell to transdifferentiate into diverse lineages
How might HSC's be involved in repair/immune?
Migrate to site of inflammation and generate innate immune cells, release GF's and cyotkines for promoting repair
Stem cells in bone marrow include? (2)
What do HSC's generate in bone marrow?
All blood cell lineages
What do MSC's generate in bone marrow?
Chondrocytes, osteoblasts, adipocytes, myoblasts, and endothelial cell precursors
Stem cells in liver are found where?
Differentiate into what
Canals of Hering (oval cells)
Hepatocytes and biliary cells
Stem cells in the brain are called what?
Neural stem cells
Where are stem cells in the skin? 3
Hair follicle bulge, interfollicular layers of epidermis, and sebaceous glands
Replication of cells in cell cycle is stimulated by what? 92)
1. Growth factors
2. Signaling from ECM components through integrins
Components of cell cycle? 4
1. G1 (presynthetic)
2. S (DNA synthesis)
3. G2 (premitotic)
4. M (mitotic phases)
When do most controls of cell cycle act?
Between G1 and S phase at restriction point
Progression in cell cycle regulated by what?
2. Cyclin-dependent kinases
What do CDK's do?
Bind and form complexes with cyclins
Phosphorylate cell cycle inhibition proteins such as RB
How does RB inhibit cell cycle?
Forms tight inactive complex with TF E2F
What will inhibit CDKs? And when?
CDK inhibitors at checkpoints
What regulates the CDK inhibitors?
Senescence or apoptosis is triggered via what?
Proliferation of cells is driven mainly by what?
What effects can growth factors have? 4
1. Promote survival
2. Affect locomotion, contractility
3. Affect cellular differentiation
4. Promote angiogenesis
How do growth factors act?
Ligands that stimulate transcription of genes
Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) share what?
Common receptor (EGFR) family of four membrane receptors with intrinsic tyrosine kinase activity
EGFR1 mutations/amplification result in what?
Cancers of lung, head, neck, breast, glioblastomas, and others
ERB B2 receptor is overexpressed in what?
Hepatocyte growth factor (HGF) has what receptor?
c-MET is highly expressed or mutated in what
Tumors of renal and thyroid papillae
HGF is identical to what?
Scatter factor for fibroblast
Is HGF important?
Required for survival during embryonic development
Platelet derived growth factor binds to what?
PDGFR alpha and Beta
Where is PDGF stored?
When is it released?
Upon platelet activation
Effect of PDGF?
Migration and proliferation of fibroblasts, smooth muscle cells, and monocytes to areas of inflammation and healing of skin wounds
How many forms of VEGF are there?
Effect of VEGF? 2
Vasculogenesis and angiogenesis in chronic inflammation, healing of wounds, and in tumors
Fibroblast growth factor includes how many members?
What is FGF-7 known as?
Keratinocyte growth factor?
What FGF works in wound repair? (2)
FGF-2 and KGF re-epithelialize skin wounds
What FGF works in angiogenesis?
What are four main functions of FGF?
Development of muscle and lung
What is a growth inhibitor for most epithelial cells?
TGF-Beta is what type of agent?
Pathologically involved in what?
Potent fibrogenic agent
Fibrosis in chronic inflammatory conditions and hypertrophic scars
Is TGF-beta involved in immune response?
Strong anti-inflammatory BUT might enhance some immune functions
What is autocrine signaling?
Cells respond to molecule that they themselves secrete
Examples of autocrine signaling? 2
What is paracrine signaling?
One cell type produces the ligand which in turn acts on adjacent cells
Example of paracrine signaling?
CT repair and wound healing
What is endocrine signaling?
Hormones synthesized by cells of endocrine organs act on target cells distant from site of synthesis
Main receptor types? (4)
1. Tyrosine kinase activity receptors
2. Receptors that recruit kinases
3. G-protein-coupled receptors
4. Steroid hormone receptors
Example of receptors with intrinsic tyrosine kinase?
1. Growth factors
Ligand binding in tyrosine kinase receptors causes what? (3)
1. Dimerization of receptor
2. Tyrosine phosphorylation
3. Activation of receptor tyrosine kinase
Example of receptors that recruit kinases?
Cytokine receptors transmit signals to nucleus by what?
G-coupled protein receptors are used by what?
How do g-coupled protein receptors transmit signals?
Trimeric GTP-binding proteins
What is the largest family of plasma membrane receptors?
G-protein coupled receptors
Defects in G-coupled receptors result in what?
Retinitis pigmentosa, corticotropin deficiencies, and hyperparathyroidism
Steroid hormone receptors are found where?
Ligands that bind to steroid hormone receptors include what? (3)
1. Thyroid hormone
2. Vitamin D
What is one special branch of steroid hormone receptors?
And they are involved in what?
Peroxisome proliferator-activated receptors
Adipogenesis, inflammation, and atherosclerosis
Transcription factors do what mainly?
Modulate gene activity
Growth promoting genes include? (2)
Cell cycle-inhibiting gene?
Why can't mammals regenerate limbs or organs?
Absence of blastema formation