– spare parts from blood stem cells can save a person’s memories and knowledge.
Scientists have made the surprising observation that bone marrow stem cells occasionally fuse with the nerve cells of the brain. Clas Johansson at CMM wants to master that process, in order to support damaged nerve cells for example from Alzheimer’s or Parkinson’s disease, or after a stroke. He has previously been given a significant stipend from the Stichting af Jochnick Foundation.
In the brain, there are billions of cells with nerve fibres intertwining in an intricate network. The connections between nerve cells form memories and store knowledge; they make a person the unique human being he or she is. If the network changes, the person does too. When someone is afflicted by brain damage, such as stroke, Alzheimer’s or Parkinson’s disease, parts of this network often die. This leaves lasting damage, and some memories and knowledge are lost forever. The brain can heal to a certain extent, but in the case of more major damage the intricate network can never be recreated.
"You can compare it to a tree that has lost all its leaves. Trying to get all the leaves on the ground to attach to exactly the right place is a challenge, to say the least. It is nigh impossible to regain the structure that you had in the brain beforehand; all that acquired knowledge you gained for example through reading books or travelling", says Clas Johansson, neurobiologist and Jochnick fellow at CMM since 2007.
In order to preserve the architecture of the brain, with all its winding threads and connections with other nerve cells, Clas Johanssons research team has the goal of being able to repair damaged nerve cells by mastering a natural cell fusion mechanism in the body. They will not be able to replace lost nerve cells, but they can substantially reduce the loss.
"This is a high risk project. But preliminary results indicate that fusion of bone marrow cells and nerve cells is more widespread than has previously been demonstrated. However, the road to clinical application is a long one", Clas Johansson says.
Similar to the way that a sperm and an egg fuse at conception, stem cells from the bone marrow occasionally merge with the nerve cells of the brain. This is a process which primarily seems to be triggered by inflammations or when the brain is damaged in some other way. Among other things, scientists have studied the cerebellum (the “little brain”) in deceased women who during their lifetime underwent a bone marrow transplant with a male donor. What they found was nerve cells in the brain with two nuclei, of which one had a Y chromosome. Therefore, it must have originated from the donated bone marrow. Women who had undergone chemotherapy during their lifetime had more nerve cells with two nuclei. This could be a sign that the process has developed during evolution to repair brain cells when there is a risk of brain damage. Clas Johansson has obtained similar results in animal tests. Mice that suffer MS-like damages in the brain get more brain cells with two nuclei.
To Clas Johansson, however, it really does not matter if the process is natural or not. The main thing is that he and his research team learn to regulate it. They can then initiate a repair of the brain right after the stroke, for example.
"In an initial stage, you could administer a drug which pushes the bone marrow to produce cells that can fuse with the damaged brain cells", he says.
When cells fuse, the damaged nerve cell can get spare parts from the bone marrow cell, especially a new healthy nucleus. This is the “control room” of the cell, where all DNA is located. If the damaged nerve cell gets a new, undamaged nucleus it can live on since the new nucleus contributes with healthy genes.
One alternative treatment could be to transplant new cells to the brain or to activate endogenous nerve stem cells. The challenge remains however; how can you get the new nerve cells to form a new network which mirrors what has been lost.
Clas Johansson’s research is possible thanks to a sizeable donation from the Jochnick Foundation. With the assistance of this donation, two full time research positions could be established at CMM. These gave young scientists the freedom to do research full time. Initially, the intention was that the positions would last for three years, but the foundation chose to extend the grants for another two years. Clas Johansson hopes that in the future, his research will be able to help people who suffer from Parkinson’s and Alzheimer’s diseases as well as Lou Gehrig's disease to preserve the unique network built by the nerve cells in the brain and bone marrow.
CMM:s second Jochnick Fellow is Rickard Glas. He studies a protein which influences tumour growth in cancer.
Text: Ann Fernholm