BME Final Review

Obtained directly form animal tissue

Ex: Take skin off your arm and put it in a petri dish

after the 1st passage of the primary culture

Ex: Move the skin cells from the 1st petri dish to a new one

Cell lines have LIMITED proliferation because A PROGRESSIVE SHORTENING OF TELOMERES

By uptake of new genetic material

Loss of functional Rb or p53, overexpression of telomerase

Amplification of stem-cell pool

Maintenance of stem-cell pool

Diminution of stem-cell pool

2 stem cells

2 stem cells: one the replenishes the pool and the other goes and differentiate

1 stem cells that replenishes the pool and 1 progenitor cell

1 stem cells that replenishes the pool and the other daughter cell dies

This allows you to keep healing yourself if you get scratched, rather then just being able to healing yourself once

The stem cell just leaves

2 progenitor cells

1 stem cells goes and differentiate and 1 progenitor cell

1 progenitor cell and the other daughter cell dies

When a cell divides and each of the daughter cells share different fates

Common of stem cells to divide into 1 daughter cell and 1 stem cell, allowing for differentiation while maintaining the “stemness”

When a stem cell divides, the daughter cell(s) fate is determined by their subsequent environments

When a stem cell divides, the daughter cells have internal asymmetry endowed to them at the time of division which determines fate

Stem cells have the ability to differentiate into any cell type in the body, while progenitor cells are more limited in their differentiation potential and can only develop into specific cell types.

Also stem cells can self renew…progenitor cells don’t

Hematopoietic stem cells found at the earliest stage of development in the bone marrow

1. Interstation of a long needle to the middle of the bone

2. Chemically-induced migration of stem cells into the blood and then collection from the blood. 

Stores the stem cells that create blood cells and platelets

Amount decreases with age (which is why you need recovery time between donating blood)

Store fat

Amount increases with age

Hematopoietic stem cells collected from circulating blood rather than from bone marrow

Less painful procedure

Some medical conditions exist where a patient cannot accept a bone marrow transplant

For allogenic: hematopoietic and immune recovery are faster

For autologous: faster blood count recovery

Increased cost and complexity of collection procedures.

Need a lot more donors (10 times from 10 people) or need to chemically induce the migration of more into in the donors body

Undifferentiated cells that can become all types of blood cells

Specific signal proteins or accompanied by specific cells that produce these proteins

Bone marrow stromal cells

Supporting growth medium

Generate signal molecules that command the stem cells to rain undifferentiated or to commit to differentiation

Using specific growth factors and proteins

Through the isolation and targeted manipulation of cells, we are finding ways to identify young, regenerating cells that can be used to replace damaged or dead tissue

Treatment consists of the transplantation of cells rather than fully functioning tissue

Identifying usable cells for cell therapies

Cell must “learn” to function with bodily tissue

Immune rejection

Cancer

Osteogenic cells

Osteoblasts

Osteoclasts

Osteocytes

Bone-lining cells

Respond to trauma, give rise to new osteoblasts and osteoclasts that can reform and remodel bone

• G in “genic” stands for “give rise”

Bone-forming cells that synthesize and secrete new bone matrix

• B in “blasts” stands for “bone matrix”

Large, multinuclear cells that enzymatically breakdown bone tissue, remodel and help heal damage

• Cl in “clasts” stands for “Can’t Live”

Mature cells that have secreted bone tissue around themselves; maintain bone health, through enzymatic secretion, influence mineral concentrations and regulate calcium release into the blood-stream

Found along the surface of adult bone; thought to regulate the movement of calcium and phosphate into and out of the bone matrix

Tissue engineering modalities that should provide a in vitro environment for rapid and orderly development of functional 3-D tissue structures

Establish spatially uniform concentrations of cells with in the 3-D scaffold

Control culture conditions (temperature, pH, osmolality, oxygen, nutrients metabolites, growth factors, etc.)

Facilitate mass transfer between cells and culture environment

Provide physiologically relevant physical signals

dX/dt=μx → X(t)=X(0)e^(μt)

μ=ln(2)/t(d)

μ = specific growth rate

t(d) = doubling time

X(t) = number of cells at time t

t = time

X(0) = initial number of cells

the number of cells in the population

how frequently the cells divide

Some cell populations grow exponentially, but may stop growing when room to expand runs out (contact inhibition)

μ=0.252 day^(-1)

td = 2.73days

Kd = [G][R]/[G:R]

[G:R]/Rtotal = [G]/([G]+Kd)

[G} = Concentration of growth factor

[R] = concentration of receptor

[G:R] = concentration of bound complexes

Kd = dissociation coefficient

Receptor occupancy rates need to be between 25-50%

If you know the dissociation constant for a signaling molecule and its receptor, you can determine what minimum concentration of the signaling molecule needs to be around the receiving cell in order to have significant cellular response

[G] = 12.7nM

To achieve 50% occupancy, the concentration of the signaling molecule must be the same as the dissociation constant

Driven by pressure differences (such as blood flow)

Created the flow that transports molecules in the blood to all parts of the body

Mediated by concentration gradients (such as the case in endothelial cell migration and proliferation)

Promotes molecules to exit the blood into the tissues and vice versa

contain semipermeable membranes that block immune components form entering and disrupting the device

Small pores so immune system components cannot get in but glucose can

Larger pore size

Allow free transport of molecules and host cells between the body and the implant (biodegradable implants)

pore size

size distribution

continuity of the individual pores

Death of the surrounding tissues

Replacement by the surrounding tissues

• Sutures

Formation of a non-adherent thin fibrous capsule

• Green film on breast implant

Formation of a interfacial bond with surrounding tissues

Becomes part of the body

Stress = force/cross-sectional area

Strain = [(deformed length - original length)/(original length)] * 100%

Youngs Modulus = Stress/Strain

Tells you:

Stiffness

Yield Strength

Ultimate tensile strength

Toughness

Failure Strain

Like bone

High yield strength

Breaks Easily

Like tendon

Low yield strength

Tough

Stretching the material until failure

Bending the material until failure

Use atomic force microscopy to map stiffness at the nanoscale

Subjecting the material to cyclic stress below the UTS to see how the material endures over time

Solubility

Permeability

Stability

• can be tailored chemically or by how the drug system is inherently engineered

Hydrophobic drugs can be DELIVERED IN LIPOSOMES to improve solubility

PEGylation

Encapsulation in phospholipid carrier (liposome)

Backbone modification

The conjugation of the drug to poly(ethylene glycol) polymers which can improve solubility based on the length of the polymer chain

Increases stability (slower excretion)

Involves ability to enter membrane-separated compartments

Large side chain modifications decrease enzymatic reaction rate, therefore increasing stabiity to liver-mediated excretion

PEGylation

Liposome encapsulation

liposomes have bee used as a platform for drug delivery for many years

The surface of the liposome can be functionalized to enhance specific properties

Combination of therapeutant and diagnostic functions

Covalently bonded molecules can offer specific targeting functions

Used to image soft tissue

MRI uses radio wave pulses to excite the nuclei of hydrogen atoms into a higher energy state

When protons relax to lower energy states, they release a photon equal in energy to the gap between higher and lower energy states

Photons are detected by an antenna coil (electromagnetic induction) in the MRI system

Higher signals correspond to faster relaxation and higher proton density

MRI utilizes magnetism and water content, and since soft tissue

contains more water than bone, it is easily distinguished

Suited of bones

Bone strongly absorbs X-ray beams, creating the shadow image we can use to diagnose fractures

X-rays employ the use of X-ray beams that soft tissue cannot absorb well, if at all. All soft tissue looks the same on X-ray images.

MRI employs strong magnets that align the water molecules in our tissues. Soft tissues have higher water content than hard tissues, and each soft tissue has its own respective water content. When and MRI machine pulses radio waves through our bodies, the water molecules will be knocked off of their alignment. The machine detects the energy released during realignment, allowing us to visualize soft tissues with greater intensity than harder tissues. Realignment mechanisms also differ between soft tissue (hydrogen atoms in each tissue do not realign at the same pace or in the same direction. These differences can help MRI distinguish between types of soft tissue.

measure of radiation quantity and its effect on surrounding objects (radioactive exposure)

defines the number of disintegrations per unit time (radioactive activity)

The two are used in conjunction with each other, as where there are roentgen, there are curies, but are not interchangeable

T(1/2) = ln(2)/lamda

N(t)/N(0)=e^(-lamda*t)

lamda = decay constant

t = time

t(1/2) = half-life

Constant

It is unaffected by temperature, pressure, or chemical combination

The process in which the number of atoms are reduced through disintegration of their nuclei

A characteristic of all radioactive materials