Day 1 stem cells: The science
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BY MARK ANDERSEN / Lincoln Journal Star
Look closely at the human body.
Closer still.
Use a microscope.
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As stem cell research dominates the headlines with advances in the laboratory and a political standoff in Washington, the Journal Star takes a look at its imprint in Nebraska.
Sunday, June 17
THE SCIENCE: Learn about stem cells, the flexible building blocks from which each human being is constructed.
THE RESEARCHER: We’ll introduce you to Dr. Stephen Rennard, a researcher working with embryonic stem cells at the University of Nebraska Medical Center in Omaha.
Monday
THE POLICY: Regents discuss the rules adopted in 2001 that guide research at the University of Nebraska.
Tuesday
THE ETHICS: Supporters and opponents of embryonic stem cell research have the same information. They just don’t agree on an interpretation.
Wednesday
THE BENEFICIARIES: As politicians debate the necessity of embryonic stem cell research, Ben Stahl waits and hopes. Also, where research likely will first be useful.
Thursday
THE POLITICS: Stem cell research likely will play an increasing role at the ballot box. Also, the difference between adult and embryonic stem cells and what the latest scientific discovery means.
Friday
RESEARCHER 2: Meet Dr. Ira Fox, the other UNMC researcher using dated human embryonic stem cell lines to look for cures for liver disease. Also, how the body creates replacement cells.
Sunday, June 24
FUTURE OF THE MED CENTER: If UNMC wants a successful future, do its researchers need to study stem cells?
***
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At this range, the body no longer appears as a single entity but as a collection of very different actors.
Each individual human cell plays a specific role.
The survival of them all depends upon the coordinated contribution of the individuals.
Too few blood cells and phhttt … it’s over.
Too few bone cells and crunch.
Too few nerve cells and, uhh, I forget.
The tiny contribution of each cell combines with others like it.
A single nerve transmits one impulse. Many impulses bunch into a signal. Signals merge to become a thought.
Together, the cells become us.
But we will always be the individual cells.
Death eventually will come because some group of cells will stop doing its job.
The system will break down. Blood won’t flow. All cells will die — and us with them.
From one to trillions
It takes trillions of cells to make an adult body.
And every one of those cells descended from one original cell.
Actually, from two halves of that one cell.
Half came from a mother’s egg.
Half from a father’s sperm.
They united to form the one cell.
It became two cells, then four, then eight, and quickly there were thousands, billions, trillions.
That first cell was a stem cell. Amid the trillions of actors in an adult, there will be many other stem cells — but none like that first one.
These later stem cells will continue dividing until we die, making new cells, replacing those turning to dust.
The cell lumberyard
Look closely at the cell.
It’s built of proteins that act a lot like bricks, steel and 2-by-4s.
Proteins are chemical chains that join together. They’re like prefabricated building blocks.
Existing cells create all the proteins used to make new cells.
About 30,000 different proteins must be created to build all of the different cells of the human body.
Many proteins get altered by chemical saws and welders once they reach the job site.
Thus, the body ends up with more than 200,000 unique shapes to use in constructing its trillions of cells.
How the materials — the proteins — fit together determines whether they’ll form part of a cell’s walls, its doors, an elevator or power plant.
Inside each cell, proteins zip around on conveyor belts. Sugars are burned.
Cells contain fuel storage depots, data centers, maintenance shops, shipping, receiving and communications departments.
Place any of these out of sequence, and the factory can fail.
If a conveyor belt ends at a stairwell, materials will clog the exit. The cell may even blow up.
Factories gone bad are supposed to blow up. Nature doesn’t want its failures creating new cells.
The need for each cell to survive as a small factory and yet support the larger system never changes.
A muscle cell survives unto itself, but it also contracts, contributing to the body’s movement.
A nerve cell survives unto itself as well, but it also transmits a signal.
What changes, especially early on, is the complexity of the system comprised by all of the cells.
In the early days when there’s a handful of cells from a newly united sperm and egg, the system — the body — is simple.
Cells can survive on stray bits of energy lying around on a plastic dish.
Later, increasingly complex systems must circulate oxygen and sugars and dispose of waste.
Cell factory renovations
As cells multiply over successive generations, new factories will differ from their predecessors.
By the time the body has moved from the one original cell to become a collection of trillions, there will be nerve cells and blood cells, bone cells and liver cells.
By then, the cell systems will have combined to form even bigger and more complex systems.
The cell factories still toil independently, but together they form tissues, like heart muscle. The tissues work together to form organs, like the heart. And together the organs form us.
Cells may begin to differ as early as that first division of the original cell.
By the time there’s a tiny ball of 30 cells, some have chosen to become the outside cells.
Still identical in appearance, others have chosen to become middle cells.
From plans to buildings
Written instructions for this increasingly complex interaction of factories exists within the original cell. It’s in the chemical code called DNA.
The exact same written instructions exist in the trillions of adult body cells.
Contained within these written instructions are the patterns for all 30,000 intermediate-stage proteins.
No one cell uses all of these proteins. One type of cell will use one set. Another will use a different set. There may be overlap.
As a cell divides and chooses a direction, its protein formula changes. New materials result in new shapes — new parts — and changed parts change the factory workings.
Changes that occur from one generation to the next may not be great. It may be more like a remodeling than an overhaul.
To review: Cells are three-dimensional living factories.
The DNA is the plans, the blueprints.
There’s a strong connection between the plans for a factory and the factory itself, but they’re not the same thing.
The DNA library
Building a system with trillions of cells operating together obviously requires a huge set of plans.
It’s helpful to think of it as a library of plans, a library with many rooms.
Each room contains the patterns needed to make all of the proteins for just one type of cell.
The library’s rooms are arranged in rings.
In this scheme, the plans of the original fertilized egg lie in the center room.
The offspring of this original cell can use the plans from this room or plans from an adjoining room in the next ring.
Their descendant cells will have the same option: plans from the room of their parent or plans from adjoining rooms in the next ring.
The only closed direction is back toward the center. Cell development always moves toward the more specialized.
A cell democracy
To the body, it doesn’t matter which cells stay in a same room and which move on to the next circle.
It matters only that some do change and some don’t, and that changes occur in the right proportions.
Eventually, there must be enough heart, brain and bone cells to take up the posts necessary for the body to survive.
There’s no general contractor overseeing system development.
And no one cell coordinates the progression. It’s a joint effort.
Cells communicate constantly with other cells around them.
To do so, they emit chemical signals, like smoke signals, into their shared liquid surroundings.
They also sample the levels of other chemicals present in the background.
Many types of communication occur simultaneously and in different languages. It’s like a symphony of lights, smells and sounds.
Individual cells experience the performance differently depending on whether they have front-row seats or are tucked into the balcony.
The real determining factor for what new type of cell is created is location, location, location.
Inside the cells, the unique experience causes some doors leading to an outer ring of the DNA library to slam shut and others to open.
Inside one factory, a hinge that was laid down for later placement of a factory door instead will be removed. This line of cells doesn’t need a door there.
So try as they might, scientists working with this cell might be unable to force it to accept a door. There’s no longer a hinge.
In working with stem cells, it almost always will be easier for researchers to force cells down a path that mimics their natural progression.
On the other hand, it will be more difficult to force a cell to step back and rebuild a hinge so it can later accept a door.
The lost factories
Throughout life, there will be great demand for certain types of factories. Skin cells last only five days, so their factories must continue at full production.
Other types of cells will be produced mostly in the womb or during early childhood. Most nerve cells must last a lifetime.
The goal of embryonic stem cell therapy, then, is to take cells from a recently fertilized egg, those at the beginning of the development process, and push them along a path they might have followed in a developing fetus.
The goal is to push them into becoming brain cells, pancreatic beta cells, heart muscle cells, the types of cells not created in large numbers by an adult body. The premature demise of these irreplaceable cells causes Parkinson’s disease, diabetes, heart failure.
A stem cell is any type of cell that can forever produce the more specialized cells needed by the body.
Not every stem cell holds within it the full range of possibilities.
Some can make blood.
Some can make nerves.
But that first cell, the newly fertilized egg, is a stem cell capable of producing all of the other cells.
Adult stem cells can be pushed in far fewer directions. Still, they have been used in novel ways.
For example, adult blood stem cells have been manipulated to produce heart muscle cells.
Moved from their home in the bone marrow and placed in the heart, blood stem cells receive different signals from their new surroundings. It could be that these signals force blood stem cells to create new muscle cells.
Another possibility is beginning to appear more likely. Blood stem cells placed in a damaged heart also emit signals.
These signals may be causing surviving muscle stem cells to reactivate local production.
If the therapy works for you, what’s the difference?
Inquiring scientists want to know.
Reach Mark Andersen at 473-7238 or mandersen@journalstar.com.
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