Tissue repair (1 of 4)

What will we discuss today?

• General principles of cell proliferation

• Stem cells

Robbins basic pathology 9th edition

Cell number determinants

Cells that proliferate in repair

• Tissue remnants

• Endothelial cells

• fibroblasts

Depending on polypeptide growth factors

The cell cycle

Non-dividing cells are in cycle arrest in G1 phase or exited the cycle (G0)

GFs, cyclins and cyclin-dependent kinases…cell cycle progression

Different proliferative capacities of tissues

• Labile tissues…continuously dividing

…continuous loss and replacement (renewal)

• Stable tissues…quiescent with only minimal replicative activity

…capable to proliferate in response to injury or decrease in tissue

mass…minimal capability in general (except ….)

…parenchyma of most solid organs

…endothelial cells, fibroblasts, and smooth muscle cells

especially in wound healing

Different proliferative capacities of tissues, cont’d

• Permanent tissues…non-proliferative

…repair is dominated by fibrosis (scarring)

…cardiac muscle, neurons and skeletal muscle

…what are satellite cells?

Stem cells

• 2 important properties:

-self renewal capacity

-asymmetric replication

when a stem cell divides, one daughter cell enters

a differentiation pathway and gives rise to mature

cells, while the other remains an undifferentiated

stem cell that retains its self-renewal capacity

2 major types of stem cells

• Embryonic stem cells (ES cells)

…the most undifferentiated

…present in inner cell mass of the blastocyst

…extensive renewal capacity

…can be maintained in culture for over a year without differentiation

Can be induced to differentiate into any of the 3 germ cell layers

2 major types of stem cells, cont’d

• Adult stem cells… = tissue stem cells

…less undifferentiated

…within organs/tissues

…restricted lineage potential

Stem cells, cont’d

• They need special niches (stem cell niches)

…examples of stem cell niches:

-brain: subventricular zone & dentate gyrus

-skin: -basal layer

-bulge region of hair follicle

-cornea: limbus

Stem cell niches

Robbins and Cotran pathologic basis of disease 9th edition

Experiments

• Hematopoietic stem cells are the most studied

…taken from bone marrow or from blood

…used for treating leukemia and lymphoma

Needs mobilization by the administration of granulocyte colony stimulating factor (G-CSF)

What is regenerative medicine?

Experiments, continued

• ES cells:

…from blastocyst (usually by in vitro fertilization)

…rejection is a problem (tissue incompatibility due to HLA molecules

on donor cells)

Introduction of genes into fully differentiated cells, such as fibroblasts or skin epithelial cells from the patient reprogramming of the somatic cell nucleus

the cells acquire many of the properties of ES cells

…the new cells are called induced pluripotent stem cells (iPS cells)

To solve the problem

Robbins basic pathology 9th edition