Thursday, January 15, 2015

Stem Cells Champion the Fight Against Brain Tumors

“A stand can be made against invasion by an army; no stand can be made against invasion by an idea." Victor Hugo, 1852.

To make a stand against brain tumors, Karen S. Aboody and her coworkers have enlisted a stem cell army.

While scientists have an unprecedented appreciation of tumor biology and doctors have a fantastic arsenal to treat most other cancers, the treatment of brain tumors is at a standstill. This unfortunate reality has frustrated brain tumor patients and their families for years.

Typically a brain tumor is surgically removed before radiation and perhaps chemotherapy. Understandably, aggressive surgery and radiation can result in damage to fragile brain tissues.  This can lead to a great deal of suffering.  A few added months of life can come with the high price of reduced physical and decision-making ability.

It is impossible for a neurosurgeon to find and remove every microscopic tumor cell from a patient.  And brain cancer cells are notorious for their ability to make their way into healthy tissues - well beyond apparent tumor boundaries. Therefore, brain tumors inevitably grow again, leading to the dismal prospects faced by most brain tumor patients.

The drawback of chemotherapy, on the other hand, is the formidable obstacle posed by what is called the blood brain barrier.  This protective lining of tissue and cells can effectively keep most cancer drugs out of the brain and in the bloodstream.  Therapies need to be specially designed to allow them access to the brain.  And for those drugs that get into brain tissue, the question of how to deliver them to the tumor still remains?

From Wikimedia Commons

A way to “seek and destroy” brain tumor cells may be what is needed to tackle the challenges to standard therapies and surgery posed brain tumors.  Advances in medical science may soon make this idea a possibility.

Karen Aboody and her colleagues have been working on a “cell based drug delivery system” that seems to hunt down cancer cells in the brain and deliver localized and effective chemotherapy exactly where it is needed. 

This group began working with the knowledge that neural stem cells can travel to sites of brain injury. Neural stem cells are immature cells that can reproduce themselves and also develop into the wide variety of specialized cells, such as neurons and other cells that make up the central nervous system.

Karen Aboody and her co-workers began by studying mice growing experimental brain tumors.  If they injected neural stem cells directly into brain tumors they found that the neural stem cells distributed themselves throughout the tumor.  If the tumors grew, the stem cells were able to spread along with them. When they injected neural stem cells into a healthy part of the brain, the neural stem cells migrated through the healthy brain tissue to find the cancer.  And when neural stem cells were injected into the blood stream, they homed to the brain, crossed the blood brain barrier and traveled directly to the tumor.  If multiple tumors were present, the stem cells tracked down and set up shop in each one. The neural stem cells even honed in on the deadly invading brain tumor cells that so easily evade the neurosurgeon during surgery.

Next, the researchers tested if neural stem cells could be engineered to produce foreign proteins.  For this part of their work, they chose a protein called cytosine deaminase.  Cytosine deaminase can cross the blood brain barrier and can activate a benign pro-drug called 5-fluorocytosine into toxic, cancer killing, 5-fluorouracil.  Changing the neural stem cells in this way did not seem to affect their brain cancer seeking abilities. When Aboody and her coworkers used their specially designed neural stem cells and injected 5-fluorocytosine into the bloodstream of experimental mice harboring brain tumors, they discovered the brain tumors decreased in size and number.

The scientists suggest that their work is evidence that a cell-based targeted therapeutic delivery system for brain tumor patients is possible.  While it might take a long time for this new approach to arrive in the clinic, the idea of having such a therapy available for the future anti-brain cancer arsenal is encouraging.

1) Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakfield XO, Snyder EY. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA, 97:(23) 12846-51 (2000).

Read about it here.