Stem Cells to Treat Spinal Cord Injury

Journal Club: Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

Written by DePaul, et al. in the journal Scientific Reports. The complete article is here.

Background: Stem cells are unique in that they can divide indefinitely and can turn into multiple different types of cells (see image below).  For example, during human development, embryonic stem cells have the ability to turn into all of the different cell types throughout the body – such as liver cells, lung cells, and skin cells. Embryonic stem cells are called pluripotent stem cells for this reason.  Stem cells have also been found in adults, but they are usually able to turn into only one or several types of cells (called multipotent stem cells).  Scientists have thought that this ability for stem cells to continually grow and turn into different cell types could be harnessed to treat a number of diseases that involve cell death, including spinal cord injury.

Stem cells - wikipedia

By OpenStax College [CC BY 3.0], via Wikimedia Commons


The authors of this paper are interested spinal cord injury (SCI).  When the spinal cord (the bundle of nerves that goes down your back) is injured when something disrupts the vertebrae (like it being hit during a car accident) this can tear or push on the spinal cord.  This causes damage to the nerves and prevents electrical signals between the body and the brain from being transmitted properly, often resulting in paralysis. The authors were interested in studying whether stem cells could help reverse the damage that’s caused by this type of injury.

Results: In this publication, the authors isolate stem cells called multipotent adult progenitor cells (MAPCs) from the bone marrow. To break this down, “multipotent” means that the stem cells can turn into several different cell types. “Progenitor” cells are actually more specified than stem cells – stem cells can divide forever, but progenitor cells can only divide a certain number of times. “Adult” means that these cells are taken from the adult bone marrow.

Because you can’t just inject cells into humans with spinal cord injury (that would have to be a clinical trial WAY down the road once there is evidence that it works in animals), the authors use a “model” of spinal cord injury in rats. Technically – they crush the rat’s spine (eek).  In case you’re interested, here’s the device they use to do this. The rat then has decreased mobility and inability to urinate on it’s own – like what might happen in the case of a paralyzed person with a spinal cord injury.

The researchers injected multipotent adult progenitor cells into the rat after injury to see if they reverse these mobility and urination effects.  Interestingly, when MAPCs are injected into a rat vein the day of injury, nothing happened. However, if the MAPCs are injected 1 day after injury, the rats recover some mobility and the ability to urinate on their own compared to rats without treatment.

One might assume that the MAPCs do this by going to the injured area of the spinal cord and re-growing nerve cells.  However, the authors found that this wasn’t the case.  In fact, the MAPCs moved to the outside edges of the injury and even more to the spleen (see image below).  The spleen is where many of the body’s immune cells are stored. In spinal cord injury, the immune system is a double-edged sword.  The immune system cleans up the damage from the injury itself but also attacks the injury and makes more damage.  There is evidence from this paper that the MAPCs in the spleen decrease the damaging effect on the spinal cord injury from the immune cells in the spleen.

figure 6 SCI

Figure 6 from the paper. The green dots are labeled multipotent adult progenitor cells (MAPCs). They are labeled green so that you can see where they are located in the rat’s body.

Conclusion: This paper presents a promising result that provides hope for this type of therapy in spinal cord injury patients.

Sci Snippet: Cancer vs. Tumor: What’s the difference?

It doesn’t matter to you what word you hear if you or a loved one is told by a doctor, “You have cancer” versus “You have a tumor.” Either way, there’s a wave of fear that is likely sustained through months, years, or a lifetime of treatment. It’s a diagnosis that nearly everyone has been touched by, so it’s something that everyone has talked about at one time or another.  The words tumor and cancer are typically used interchangeably, especially by people who are not in healthcare.  But it helps to know that there is an important distinction between cancer and a tumor when describing a mass of cells growing somewhere in the body.

The most important point is that a tumor DOES NOT mean cancer.  A tumor is a whole bunch of cells growing out of control (think of it as the cell turning on the gas pedal for cell division) creating a mass somewhere in the body.  Cancer, on the other hand, means that these cells have the potential to move and invade other parts of the body.A tumor can be benign (not cancer) or malignant (cancer).

Image of a benign meningioma. Thanks to Wikipedia for the image.

Image of a benign meningioma. Thanks to Wikipedia for the image.

What does it mean to be benign? A benign tumor still a huge mass of cells, and even though it may not spread to other parts of the body (the definition of malignancy and cancer), the mass could grow so large it presses against vital organs requiring surgical removal or causing death.  An example of a benign tumor is a meningioma.  This is a brain tumor that grows out of the covering of the brain and spinal cord, called the meninges, and although they do not typically spread to other places in the body (so they are not considered cancer), they do put pressure on the brain and spinal cord and usually have to be removed and may be treated with radiation.

benign_malignant

Thanks MedicineNet.com for the image

Cancer, on the other hand, is a tumor that has the potential to spread to other parts of the body, which is called malignancy.  This is one of the reasons that cancer is called cancer – from the Greek meaning crab because of the crab-leg like projections that are found in tumors that are invading neighboring tissue.  Tumors may be benign, malignant, or transition from something benign to something malignant.  For example, in the breast, masses of cells can form like papillomas that are a benign tumor that will not spread to other areas of the body. However, a breast cancer diagnosis implies that the breast tumor has the possibility to spread.  The only way to know whether a lump is a papilloma, breast cancer or something else is through a doctor and a biopsy.

It’s also important to note that not all cancers involve a tumor.  A great example of this are blood cancers that involve the increased growth of a particular type of blood cells, but will not have a tumor.

And in case you’re wondering where cysts fit into this, these are sacks filled with fluid, air or some semi-solid material. Cysts can be caused by a number of things including infection or clogging of glands. They may indicate a risk factor for a tumor or cancer, but are not cancerous themselves.

 

Sci Snippet – The bug that causes ulcers

Everyone can understand that bacteria can cause a disease through infection. Bacterial infections can cause huge inflammatory responses known as sepsis or result in a cut getting infected. But a bacterial infection causing ulcers? That seems weird.

Hpylori

H. Pylori under an electron microscope

This is a crazy story, but resulted in the 2005 Nobel Prize in Physiology and Medicine. In the 1980s, Dr. Barry Marshall found that the bacteria H. Pylori is often found in people with peptic ulcers. At this point, scientists didn’t even think that bacteria could survive in the acidic environment of the stomach, much less cause a disease. Ulcers were obviously caused by stress or spicy foods or too much acid. Dr. Marshall was convinced of his hypothesis and went to test his theory in pigs, but for some reason he wasn’t able to get the H. Pylori bacteria to infect the pigs.  So one night, he drank an entire petri dish of cultured H. Pylori. As a side note – it is NOT a good idea to do experiments on yourself because you have no idea what will happen (movies have confirmed this over and over). However, three days later, he felt nauseous, after a week he started vomiting and an endoscopy found massive inflammation indicative of gastritis, and two weeks later he started taking antibiotics for the H. Pylori infection. He  was the first to definitively prove that this bacterial infection caused gastritis. Although this particular experiment did not prove that H.Pylori caused ulcers, it’s now been shown by other researchers.

In fact, now scientists know that H. Pylori bacteria is found in the stomach of about 50% of the world’s population, but in most people it doesn’t cause much of an issue. 80% of people infected don’t have any symptoms and it may actually help protect against other diseases such as acid reflux and Barrett’s esophagus. However, of those infected, they have a 10-20% lifetime risk of developing an ulcer and a 1-2% risk of developing stomach cancer. What this means is that eliminating H. Pylori by antibiotics can help treat the ulcer, and can also decrease the risk of stomach cancer.

For more Sci Snippets, click here.

What is that? A beautiful image of deadly tumor cells

the eye

Thanks to Dr. Roberto Fiorelli of Barrow Neurological Institute for sharing this stunning image

It looks like an eye.  Perhaps a terrifying pink eye, like the Eye of Sauron, coming out of the darkness. It’s not an eye, but it is a bit terrifying. This is an image of a slice of the brain showing tumor cells (in green and red) surrounding a blood vessel.  How does this type of image get made?  How does this type of image help scientists? What does it mean that these tumor cells are near a blood vessel?

This image is created with a microscope – specifically a confocal microscope. I’m going to use a very weird analogy to explain why confocal microscopy is so cool, so stick with me. Imagine that you have a jello mold with an object it and you want to know exactly what the object looks like.  Now imagine a regular microscope is like a flashlight.  When you point the flashlight at the jello mold the whole thing lights up including what’s in front of the object, and if the object is translucent, the jello behind the object lights up too.  This gives you an idea of what the object is, but it may be kind of fuzzy because of all the jello you see in front and behind the object.  Confocal microscopy, on the other hand, is designed to turn that wide flashlight beam into a single pinpoint of light so only one part of the object is illuminated at a time.  So when you move this single pinpoint around (back and forth and up and down) over the object, you can get a clear a crisp image of what is inside the jello.

confocal_microscopy

To bring this analogy back into the science-verse, the jello is a cell or a piece of human tissue with layers of many cells.  The objects inside the jello are certain proteins marked so that they light up in different colors (what we call fluorescence) when excited by the light from the laser (flashlight). When confocal microscopy is used to look at these proteins, you can see clear crisp images of exactly where the proteins are in the cells.  And if you take enough images up and down through the cells and the tissue, you can even create a 3D image of the cell or a piece of tissue. Check out this neat video of a 3D rendering of a piece of the brain called the hippocampus.

Now back to the image above.  This is a piece of tissue taken from a patient with an ependymoma, a tumor derived from brain tissue and is primarily found in younger patients.  The colors you see are:

  1. Blue: a chemical called DAPI (or 4′,6-Diamidino-2-Phenylindole, Dihydrochloride) that binds to DNA. Since DNA is found in the nucleus of every cell, staining cells with DAPI helps you to locate each cell in the image – each blue dot is one cell.
  2. Red: stains a protein called GFAP (Glial Fibrillary Acidic Protein) that is found in different cells of the brain, but is also a marker of particular brain tumors, like ependymomas
  3. Green: stains a protein called vimentin that is also found in different cells of the brain, including cells that make up large blood vessels and brain tumors like ependoymomas

So what are we able to learn from this beautiful picture?  See how there are a lot of red and green cells surrounding an empty round space.  That round space is a blood vessel. Cancer cells need food and oxygen to grow, so the green and red cancer cells are clustering around the blood vessel to get the nutrients they need. Even though this is a beautiful image, it helps scientists to understand how these deadly tumors function within the brain and how they find the resources to grow.

If you want to look at more amazing images taken using confocal microscopy and fluorescently tagged proteins, check out these links

Wellcome Image Awards 2015
The Cell: An Image Library

Thanks to Dr. Roberto Fiorelli of Barrow Neurological Institute for sharing this stunning image from his postdoctoral work in Dr. Nadar Sanai’s Laboratory, the Barrow Brain Tumor Research Center

For more “What is That?”, click here.

Five Ways for You to Participate in Science – Citizen Science

Bunsen_burner

The Bunsen burner I didn’t have. Thanks Wikipedia for the image

I had a chemistry set growing up.  It was small with tiny white bottles holding dry chemicals that sat perfectly on the four tiny shelves of an orange plastic rack.  My dad would let me use the workbench in the basement to do experiments – entirely unsupervised!! You might expect that I did really interesting chemical reactions, and this formative experience helped me to develop into the curious scientist that I am today. Completely wrong.  I remember following the instructions, mixing the chemicals, and then getting stuck because I didn’t have a Bunsen burner.  So many chemical reactions rely on heat, and the green candle stuck to the white plastic top of an aerosol hairspray can wasn’t going to cut it.

My main options for doing science as a kid revolved my failed chemistry experiments, my tiny microscope and slides, and a butterfly net that never netted a single butterfly (not for lack for trying).  However, today with computers (that’s right – no computer growing up – that’s how old I am!) there are hundreds if not thousands of ways for people to get involved in science, without having to invest in a Bunsen burner. This citizen science movement, relies on amateur or nonprofessional scientists crowd-sourcing scientific experiments. I’m talking large scale experiments run by grant-funded university-based scientists that have the possibility of really affecting how we understand the world around us. One example you may have heard about is the now defunct Search for Extraterrestrial Intelligence (SETI) which used people sitting at their computers to analyze radio waves looking for patterns that may be signed of extraterrestrial intelligence. They didn’t find anything, but it doesn’t mean that they wouldn’t have if the program had continued!

Here are five ways that you can become involved in science from where you’re sitting right now!

americangut1. American Gut: Learn about yours (or your dog’s) microbiome

For $99 and a sample of your poop, you will become a participant in the American Gut project. After providing a sample, the scientists will sequence the bacterial DNA to identify all of the bacterial genomes that are present in your gut.  This study already has over 4,000 participants and aims to better understand all of the bacteria that covers and is inside your body – called your microbiome – and to see how the microbiome differs or is similar between different people or between healthy people versus those who may be sick. The famous food writer Michael Pollan wrote about his experience participating this the American Gut project in the New York Times.  They are also looking at dogs and how microbiota are shared with family members, including our pets!

2. Foldit: solve puzzles for sciencefoldit

Puzzles can be infuriating, but at least they have a point to them when you get involved in the Foldit project.  Proteins are the building blocks of life.  Made out of long strings of amino acids, these strings are intricately folded in your cells to make specific 3D shapes that allow them to do their job (like break down glucose to make energy for the cell).  Foldit has you fold structures of selected proteins using tools provided in the game or ones that you create yourself.  These solutions help scientists to better predict how proteins may fold and work in nature.  Over 240,000 people have registered and 57,000 participants were credited in a 2010 publication in Nature for their help in understanding protein structure.  Read more about some of the results here.

3. EyeWire: Mapping the BrainEyeWire-Logo

The FAQs on the EyeWire website are fascinating because as they tell you that there are an estimated 84 billion neurons in the brain, they also insist that we can help map them and their connections. After a brief, easy training, you’re off the the races, working with other people to map the 3D images of neurons in the rat retina.  You win points, there are competitions, and a “happy hour” every Friday night. The goal is to help neuroscientists better understand how neurons connect to one another (the connectome).

4. Personal Genome Project: Understanding pgpyour DNA

The goal of the Personal Genome Project is to create a public database of health, genome and trait data that researchers can then use to better understand how your DNA affects your traits and your health. This project recruits subjects through their website and asks detailed medical and health questions.  Although they aren’t currently collecting samples for DNA sequencing because of lack of funding, they have already sequenced the genomes of over 3,500 participants. The ultimate goal is having public information on over 100,000 people for scientists to use.

mindcrowd5. MindCrowd: Studying memory to understand Alzheimer’s Disease

Alzheimer’s Disease is a disease of the brain and one of the first and most apparently symptoms is memory loss.  MindCrowd wants to start understanding Alzheimer’s disease by first understanding the differences in memory in the normal human brain.  It’s a quick 10 minute test – I took it and it was fun!  They are recruiting an ambitious 1 million people to take this test so that they have a huge set of data to understand normal memory.

This is a randomly selected list based on what I’m interested in and things that I’ve participate in, but you can find a much longer list of projects you can participate in on the Scientific American website or through Wikipedia.  Also, if you’re interested in learning more about the kind of science that people are doing in their own homes, the NY Times wrote an interesting article: Home Labs on the Rise for the Fun of Science.  If decide to try one out, share which one in the comments and what you think!

Book Club – A Short History of Nearly Everything

short

Thanks to Amazon for the image

A Short History of Nearly Everything by Bill Bryson is a brilliant book. Bill Bryson is known for his travel writing and humorous writing style, but it this book he focuses his talents on explaining science. He starts at the beginning looking at the advent of our universe to understanding atoms and quarks to delving into our planet to the beginnings of life itself.  In particular, he has a chapter called “Cells” that provides one of the best descriptions of cell biology written for the public that I have ever read.  A few chapters later in “The Stuff of Life” he describes DNA and genetics in an equally accessible way.  This is one of the few popular science books that I would unreservedly suggest to anyone from ages 15 to 115.

The book won numerous, well-deserved awards including the 2004  Aventis Prize for best general science book and the 2005 EU Descartes Prize for science communication.  Please feel free to continue the conversation once you read the book by commenting below or by Asking me a Question.

For more Book Club books, click here.

What is a cell? Based on a conversation with my husband

I was at an awesome brewery in Flagstaff over the weekend (shout out to Historic Brewing Company) with my husband.  Over a beer and homemade chips, we start discussing science.  Now, don’t imagine that just because I’m a scientist that I insist on talking about it all the time.  Most of the time we’re talking about our dogs or work or school or this blog.  This weekend, the science discussion actually started by taking about grading curves and how they are sometimes fair and sometimes not, and they sometimes measure student’s performance and sometime the teacher’s (sophomore year physics – I’m referring to you!).  From here, the discussion gets a bit fuzzy, but we eventually starting discussing cells and start arguing about the difference between eukaryotic and prokaryotic cells.

Before I get into the details of the argument, let’s talk about what a cell is. Cells are the lego blocks of all living organisms.  Cells contain the genetic material and can divide and replicate into new cells (in a process called the cell cycle).  If you take any part of an organism and zoom in, you will see cells. Cells don’t all look or function the same – as you may imagine because cells in your body do different thing than cells in a plant or cells in a fungus or a bacterial cell. And even different cells in your body look and function differently. Blood cells are round and flow through blood vessels.  Blood vessels are made out of multiple layers of cells surround by muscle cells to help contract and expand the vessels to move the blood. Muscle cells are different depending on where in your body they are located. For example, heart muscle cells look and function different than muscle cells found in your bicep. Nerve cells (called neurons) in the brain often have lots of branching so that they can connect to other nerve cells to transmit signals .  And just to clarify, I know I said that you could zoom into ALL parts of your body and see cells, however there are exceptions to everything.  For example, hair and nails are make out of a hard, tough protein called keratin and not cells.

shapesofcells

Thanks to Wikipedia and http://upload.wikimedia.org/wikipedia/commons/e/e5/414_Skeletal_Smooth_Cardiac.jpg

Even though cells may look different and function differently, all cells have a few things in common:

  1. All cells are surrounded by a membrane, often called the plasma membrane, that is typically made up of fats (called lipids) and proteins.  You can think of this as a plastic bag that can hold stuff inside of it.
  2. The stuff inside this cell membrane includes cytoplasm – you can think of this as a jello inside the plastic bag made up of lots of proteins.
  3. Inside all cells is the genetic material (DNA) that is required to make and replicate the cell and for the cell to function.

Even though different types of cells have different shapes and different functions, there are two main types of cells:

  1. Prokaryotic cells – these are cells that do not have membrane bound structures inside the cell membrane (floating around in the jello-like cytoplasm).
  2. Eukaryotic cells – these cells have membrane bound structures called organelles. We’ll discuss specific organelles in future posts, but some organelles that you may already be familiar with are the nucleus, which is another membrane-bound structure that contains the DNA, or mitochondria, which are the energy-producers of the cell, or chloroplasts, which are the organelle that converts sunlight into energy in plants.
kindsofcells

Thanks to Wikipedia for the images

So, if a cell has a nucleus, it’s eukaryotic and if not, it’s prokaryotic. And this is where the argument started.  My husband insisted that eukaryotic cells are defined by the fact that they are only found in multi-cellular organisms.  Multi-cellular refers to any organism that’s made up of more than one cell – like humans who have about 100 trillion cells, redwood trees, spiders, birds, seaweed, whales, algae, mushrooms, etc.  Although it is true that eukaryotic cells are mostly found in multi-cellular organisms, protists are single-celled and contain a nucleus – making them eukaryotic. Conversely, most prokaryotes are single cells – like bacteria and plankton.  However, some of these single-celled prokaryotes can stick together and work together as a community in a slimy biofilm that is very similar to being multi-cellular.

Why in the world does this matter? Why did I spend any of my energy on a Friday night (and a bit on Saturday when we rekindled the discussion) even discussing this point?  It’s because definitions matter and understanding the details matter – especially in science. But that ultimately isn’t the point of this post – it’s about cells.  Without cells, life as we know it wouldn’t exist.  Without an understanding of cells and how they work, we can’t understand what it means when they dysfunction and cause disease in humans.