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.

Are vaccinations needed after a stem cell transplant?

Vaccines are a hot topic. Vaccines bring up lots of discussion, lots of false information, and a vitriolic passion rarely seen in matters of science and pseudoscience. My first post on this topic was about what vaccines are and and what they do. My second post  addressed some of the false information and controversy (with an added bonus of bringing in my lovely sister’s fabulous point of view as a mom of two!) This post will address a question I was asked about whether or not vaccinations are needed after a stem cell transplant.

A friend of mine asked me a question about her friend with non-Hodgkins who was getting a stem cell transplant. He was wondering if he has to get all new immunizations.  Since we have been talking about what immunizations (or vaccines) are and what they do, I thought this would be the perfect place to answer this question.  Before I start, please keep in mind that I’m a doctor, but not that kind of doctor.  This is NOT a medical opinion.  Nothing that I say here should be considered medical advice or used in lieu of talking directly to a doctor.

I won’t give medical advice, but I will explain what is known biologically about why immunizations would be needed after a stem cell transplant.  I won’t go into a lot of detail (in part because I’m not an expert immunologist) but also because there are some interesting resources I can refer you to:
https://www.fredhutch.org/en/treatment/long-term-follow-up/FAQs/vaccination.html
http://en.wikipedia.org/wiki/Vaccine#Developing_immunity
http://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation

immune-system

The bone marrow is one of the main organs that makes immune cells required to mount an immune response after infection. Thanks to aids.gov for the image

Remember the description about how vaccines work.  They induce a “memory” in the immune system that recognizes the infectious agent if it is encountered and kills it before it can kill you. The cells that are responsible for the immune response and creating this “memory” are made in the bone marrow and circulate in the blood (it’s a convenient system because your circulating blood gets access to most of your body so it can find and attack infectious agents quickly).

Non-Hodgkin’s lymphoma is a blood cancer where white blood cells (also made in the bone marrow) divide out of control.  Chemotherapy, one of the main treatments for this kind of cancer, kills the cancer cells circulating in the blood but also kills cells in the bone marrow, including the stem cells responsible for making new blood and immune cells.  With high enough doses of chemotherapy, all of the stem cells in the bone marrow are killed along with the cancer cells. The stem cell transplant replaces the stem cells in the bone marrow which make new blood cells – replacing cancerous cells with healthy blood cells.  Researchers have found that the memory from immunizations often decreases after a stem cell transplant. Part of this is because the cells that have the memory may be killed as part of the chemotherapy and the new immune cells haven’t encountered the vaccine before so they won’t have the memory. Part of it may be because during treatment the patient is on immuno-suppressives.  Part of the reasons also are still being studied or aren’t very clear.

However, either way, it is suggested that immunizations are needed after the transplant – though not necessarily right after transplant.  Again, to reiterate, a doctor will have this information and will be able to provide medical advice.  I’m just giving some background as to biologically why immunizations may be needed after a stem cell transplant.